Regression of macular edema with topical brinzolamide and nepafenac alone and identification of a novel gyrate atrophy mutation / Regressão de edema macular com o uso tópico de brinzolamida e nepafenac e identificação de uma nova mutação na atrofia girata

ABSTRACT Gyrate atrophy is a rare metabolic autosomal recessive disorder caused by ornithine aminotransferase enzyme deficiency that leads to characteristic progressive, degenerative chorioretinal findings. Patients complain mostly of low vision, night blindness, and peripheral vision loss. Posterior subcapsular cataract, myopia, choroid neovascularization, and intraretinal cysts may be accompanying factors related to vision loss. We encountered a patient with vision loss secondary to posterior subcapsular cataract and intraretinal cysts. After treatment with topical brinzolamide and nepafenac (and without any diet mo dification and/or supplementation), we observed 143- and 117-mm macular thickness resolutions with 2 and 1 Snellen lines of visual gain in his right and left eyes, respectively. Also, we detected a novel homozygous mutation in the ornithine aminotransferase gene: c.1253T>C (p.Leu418Pro). Carbonic anhydrase inhibitors and/or non-steroid anti-inflammatory drugs can control macular edema in patients with gyrate atrophy-associated intraretinal cysts. The genetic variants may also be a determinant in the responsiveness to the therapy type.

RESUMO A atrofia girata é um distúrbio autossômico recessivo metabólico raro causado pela deficiência da enzima ornitina ami notransferase, que leva a achados degenerativos coriorretinianos progressivos característicos. Os pacientes queixam-se principalmente de baixa visão, cegueira noturna e perda de vi são periférica. A catarata subcapsular posterior, a miopia, a neovascularização da coróide e os cistos intrarretinianos podem ser fatores associados à perda da visão. Encontramos um paciente com perda de visão secundária à catarata subcapsular posterior e cistos intrarretinianos. Após o tratamento com brinzolamida tópica e nepafenaco (e sem modificação e/ou suplementação da dieta), observamos resoluções de espessura macular de 143 e 117 mm e com 2 e 1 linhas de Snellen de ganho visual nos olhos direito e esquerdo, respectivamente. Além disso, detectamos uma nova mutação homozigótica no gene da ornitina aminotransfera se: c.1253T>C (p.Leu418Pro). Inibidores da anidrase carbônica e/ou drogas anti-inflamatórias não esteróides podem controlar o edema macular em pacientes com cistos intrarretinianos associados à atrofia girata. As variantes genéticas também podem ser determinantes na responsividade ao tipo de terapia.

Ibuprofeno comparado con acetazolamida para prevención de mal agudo de montaña / Ibuprofen versus acetazolamide for prevention of acute mountain sickness

INTRODUCCIÓN: El mal agudo de montaña es una condición frecuente en individuos sanos, sin aclimatación que se exponen a alturas desde 2500 metros sobre el nivel del mar. Clásicamente se ha utilizado acetazolamida para prevenirlo, pero en los últimos años ha surgido evidencia a favor de ibuprofeno. Sin embargo, no está claro cuál de estos tratamientos es más efectivo. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos dos revisiones sistemáticas que en conjunto incluyeron un estudio primario, el cual corresponde a un ensayo aleatorizado. Concluimos que no es posible establecer con claridad si ibuprofeno es mejor o peor que acetazolamida debido a que la certeza de evidencia existente ha sido evaluada como muy baja.

INTRODUCTION: Acute mountain sickness is a common condition occurring in healthy subjects that undergo rapid ascent without prior acclimatization, as low as 2500 meters above sea level. The classic preventive agent has been acetazolamide, although in the last decade there has been evidence favoring ibuprofen. However, it is unclear which method is more efficient. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis) and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified two systematic reviews that included only one primary study, which is a randomized trial. We concluded it is not possible to establish whether ibuprofen is better or worse than acetazolamide because the certainty of evidence has been evaluated as very low.

Acetazolamida como tratamiento del mal agudo de montaña / Acetazolamide for the treatment of acute mountain sickness

INTRODUCCIÓN El mal agudo de montaña es la patología más prevalente relacionada con la exposición aguda a la altura, secundaria a los efectos de la hipoxia hipobárica en nuestro organismo. La acetazolamida se ha utilizado tradicionalmente para su prevención y tratamiento, sin embargo, aún existe controversia respecto al grado de utilidad que tiene este medicamento como monoterapia. MÉTODOS Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un meta análisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES Identificamos una revisión sistemática que incluyó dos estudios primarios, ambos correspondientes a ensayos aleatorizados. Concluimos que no es posible establecer con claridad si el tratamiento con acetazolamida disminuye los síntomas del mal agudo de montaña ni si aumenta el riesgo de efectos adversos, debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.

INTRODUCTION Acute mountain sickness is the most prevalent illness related to acute exposure to high altitude, secondary to the hypobaric hypoxia effects in our body. Acetazolamide has been traditionally used for its prevention and treatment, however, there is still controversy regarding the degree of usefulness of this medication as monotherapy. METHODS We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS We identified a systematic review that included two primary studies, both corresponding to randomized trials. We conclude that it is not possible to establish clearly whether treatment with acetazolamide reduces the symptoms of acute mountain disease or increases the risk of adverse effects, because the certainty of the existing evidence has been evaluated as very low.

New classes of glaucoma medical treatment

Glaucoma is a progressive degenerative disease of the optic nerve head, characterized by a specific pattern of axonal loss and visual field deterioration. This review aims at introducing the different novel pharmacologic agents for its treatment, as well as their mechanisms. Most glaucoma patients require lifelong care and individualized treatment. Intraocular pressure (IOP), which is regulated by aqueous humor production, outflow via the trabecular meshwork (parasympathomimetics only) and uveoscleral outflow pathways, is currently the only treatable target for glaucoma treatment. Conventional glaucoma medications are categorized as β blockers, α agonists, carbonic anhydrase inhibitors, parasympathomimetics, and prostaglandin analogues. The development of basic research-derived novel classes of pharmacologic agents features novel action mechanisms, which are different from those of conventional medications. New classes of recently approved or clinical trial-tested medications include Rho-kinase inhibitors, nitric oxide donors, adenosine agonists, and prostaglandin analogs targeting E-type prostanoid receptors, etc. Their integration and future development will facilitate the expansion and customization of therapeutic options.

The relationship between topical anti-glaucoma medications and the development of lacrimal drainage system obstruction / A relação entre medicamentos tópicos anti-glaucoma e o desenvolvimento de obstrução do sistema de drenagem lacrimal

ABSTRACT Purpose: To evaluate whether any topical anti-glaucoma medications increase the risk of lacrimal drainage system obstruction or whether the presence of preservatives alone is sufficient to generate obstruction. Methods: This nested case-control study compared a group of patients with lacrimal duct obstruction who received topical anti-glaucoma medications to a control group of patients without obstruction. Results: The medical records of 255 patients with glaucoma who consulted the Oculoplastic Section with complaints of watery eyes were reviewed. Among these patients, 59 exhibited lacrimal drainage obstruction. Ninety-four percent of patients with lacrimal drainage obstruction used beta-blockers, and 41% used prostaglandin analogs. A logistic regression model was used to adjust for age, sex, and the use of other medications. No significant differences were observed regarding the topical anti-glaucoma medications used between groups. Conclusion: No single topical anti-glaucoma medication demonstrated a stronger association with the development of lacrimal duct obstruction.

RESUMO Objetivo: Avaliar se algum medicamento tópico anti-glaucoma aumenta o risco de obstrução do sistema de drenagem lacrimal ou se a presença de conservantes é su fi cien te para gerar obstrução. Métodos: Este estudo de caso-controle aninhado comparou um grupo de pacientes com obstrução do ducto lacrimal que receberam medicações tópicas anti-glaucoma contra um grupo controle de pacientes sem obstrução. Resultados: Foram revistos os prontuários de 255 pacientes com glaucoma que consultaram a Seção de Oculoplástica com queixas de olhos lacrimejantes. Dentre esses pacientes, 59 apresentavam obstrução da via lacrimal de drenagem. Noventa e quatro por cento dos pacientes com obstrução usaram betabloqueadores e 41% usaram análogos de prostaglandinas. Um modelo de regressão logística foi utilizado para ajustar a idade, sexo e o uso de outros medicamentos. Não foram observadas diferenças significativas em relação às medicações tópicas anti-glaucoma usadas entre os grupos. Conclusão: Nenhum medicamento anti-glaucoma tópico único demonstrou uma associação mais forte com o desenvolvimento de obstrução do ducto lacrimal.

Ultrasound biomicroscopy in acetazolamide-induced myopic shift with appositional angle closure / Biomicroscopia ultrassônica em mudança miópica induzida por acetazolamida no fechamento de ângulo

ABSTRACT We report a case of a 49-year-old female who presented to the emergency department with blurred vision and vomiting, hours after taking two tablets of 250 mg of acetazolamide. The anterior chamber was bilaterally flat, with normal intraocular pressure in both eyes. An ultrasound biomicroscopic (UBM) examination showed bilateral ciliary effusion and complete appositional angle closure in all quadrants. Acetazolamide-induced bilateral angle closure was diagnosed. Steroid and cycloplegic therapy were initiated, and acetazolamide was discontinued. The following day, the anterior chamber had regained its volume without substantial change in the effusion size. Three weeks later, complete resolution of the ciliary effusion was verified by means of a third UBM scan.

RESUMO Relatamos um caso de uma mulher de 49 anos que se apresentou ao departamento de emergência informando visão borrada e vômitos, horas após ter tomado dois comprimidos de 250 mg de acetazolamida. A câmara anterior era bilateralmente plana com pressão intraocular normal em ambos os olhos. Um exame de biomicroscopia ultrassônica (UBM) mostrou efusão ciliar bilateral e fechamento completo do ângulo aposicional em todos os quadrantes. O bloqueio angular bilateral induzido por acetazolamida foi diagnosticado. O tratamento com esteróides e cicloplégicos foi iniciado e a acetazolamida foi descontinuada. No dia seguinte, a câmara anterior recuperou seu volume sem alterações substanciais no tamanho da efusão. Três semanas depois, a resolução completa da efusão ciliar foi verificada por meio de uma terceira biomicroscopia ultrassônica.

Experience of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in a Regional Hospital: 70 Cases in 7 Years / 대한내과학회지

BACKGROUND/AIMS: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions that frequently result in fatal outcomes. We investigated cases of SJS and TEN in a regional hospital. METHODS: From 2008 to 2014, SJS and TEN cases were enrolled retrospectively by allergy and dermatology specialists, and their clinical features and severity-of-illness score for TEN (SCORTEN) were assessed. RESULTS: During the 7-year study period, 56 SJS and 14 TEN cases were recruited. The majority (71%) were 40-70 years of age (mean age of male and female patients, 55 and 54 years, respectively). Regarding drugs, anticonvulsants (42.8%) were the most frequently causative, followed by carbonic anhydrase inhibitors (20.0%), antimicrobials (15.7%), allopurinol (7.1%), and non-steroidal anti-inflammatory drugs (7.1%). No fatal case of SJS was seen. However, 7 of the 14 patients with TEN died (50%; mean age, 67 years; 1 of 5 [20%] males and 6 of 9 females [66.7%]). The mortality rate was reflected in the SCORTEN values. Vancomycin, allopurinol, methazolamide (two cases each) and megestrol (one case) were the causative drugs in the seven fatal TEN cases. Treatment modality did not affect the likelihood of death due to TEN. CONCLUSIONS: The causative drugs of, and frequency of mortality due to, SJS and TEN should be recognized by physicians. Elderly females with TEN are at high risk of mortality. SCORTEN values reflect the mortality rate of TEN patients. Early recognition and proper management of SJS and TEN may reduce the mortality rate.

In vitro assessment of a computer-designed potential anticancer agent in cervical cancer cells

BACKGROUND: Computer-based technology is becoming increasingly essential in biological research where drug discovery programs start with the identification of suitable drug targets. 2-Methoxyestradiol (2ME2) is a 17ß-estradiol metabolite that induces apoptosis in various cancer cell lines including cervical cancer, breast cancer and multiple myeloma. Owing to 2ME2's poor in vivo bioavailability, our laboratory in silico-designed and subsequently synthesized a novel 2ME2 analogue, 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol), using receptor- and ligand molecular modeling. In this study, the biological effects of ESE-15-ol (180 nM) and its parent molecule, 2ME2 (1 µM), were assessed on morphology and apoptosis induction in cervical cancer cells. RESULTS: Transmission electron microscopy, scanning electron microscopy and polarization-optical transmitted light differential interference contrast (PlasDIC) images demonstrated morphological hallmarks of apoptosis including apoptotic bodies, shrunken cells, vacuoles, reduced cell density and cell debris. Flow cytometry analysis showed apoptosis induction by means of annexin V-FITC staining. Cell cycle analysis showed that ESE-15-ol exposure resulted in a statistically significant increase in the G2M phase (72%) compared to 2ME2 (19%). Apoptosis induction was more pronounced when cells were exposed to ESE-15-ol compared to 2ME2. Spectrophotometric analysis of caspase 8 activity demonstrated that 2ME2 and ESE-15-ol both induced caspase 8 activation by 2- and 1.7-fold respectively indicating the induction of the apoptosis. However, ESE-15-ol exerted all of the above-mentioned effects at a much lower pharmacological concentration (180 nM) compared to 2ME2 (1 µM physiological concentration). CONCLUSION: Computer-based technology is essential in drug discovery and together with in vitro studies for the evaluation of these in silico-designed compounds, drug development can be improved to be cost effective and time consuming. This study evaluated the anticancer potential of ESE-15-ol, an in silico-designed compound in vitro. Research demonstrated that ESE-15-ol exerts antiproliferative activity accompanied with apoptosis induction at a nanomolar concentration compared to the micromolar range required by 2ME2. This study is the first study to demonstrate the influence of ESE-15-ol on morphology, cell cycle progression and apoptosis induction in HeLa cells. In silico-design by means of receptor- and ligand molecular modeling is thus effective in improving compound bioavailability while preserving apoptotic activity in vitro.

Factors affecting visual loss and visual recovery in patients with pseudotumor cerebri syndrome / Fatores que influenciam na perda e na recuperação visual de pacientes com a síndrome do pseudotumor cerebral

ABSTRACT Purpose: To investigate the frequency of visual loss (VL), possible predictive factors of VL, and improvement in patients with pseudotumor cerebri (PTC) syndrome. Methods: We reviewed 50 PTC patients (43 females, seven males) who underwent neuro-ophthalmic examination at the time of diagnosis and after treatment. Demographic data, body mass index (BMI), time from symptom onset to diagnosis (TD), maximum intracranial pressure (MIP), occurrence of cerebral venous thrombosis (CVT), and treatment modalities were reviewed. VL was graded as mild, moderate, or severe on the basis of visual acuity and fields. Predictive factors for VL and improvement were assessed by regression analysis. Results: The mean ± SD age, BMI, and MIP were 35.2 ± 12.7 years, 32.0 ± 7.5 kg/cm2, and 41.9 ± 14.5 cmH2O, respectively. Visual symptoms and CVT were present in 46 and eight patients, respectively. TD (in months) was <1 in 21, 1-6 in 15, and >6 in 14 patients. Patients received medical treatment with (n=20) or without (n=30) surgery. At presentation, VL was mild in 16, moderate in 12, and severe in 22 patients. Twenty-eight patients improved and five worsened. MIP, TD, and hypertension showed a significant correlation with severe VL. The best predictive factor for severe VL was TD >6 months (p=0.04; odds ratio, 5.18). TD between 1 and 6 months was the only factor significantly associated with visual improvement (p=0.042). Conclusions: VL is common in PTC, and when severe, it is associated with a delay in diagnosis. It is frequently permanent; however, improvement may occur, particularly when diagnosed within 6 months of symptom onset. .

RESUMO Objetivo: Investigar a frequência de perda visual (PV) e os possíveis fatores preditivos para perda e para melhora visual em pacientes com a síndrome do pseudotumor cerebral (SPC). Métodos: Foram revisados 50 pacientes com SPC submetidos a exame neuroftalmológico no momento do diagnóstico e após o tratamento. Dados demográficos, índice de massa corpórea (IMC), tempo decorrido entre o início dos sintomas e o diagnóstico (TD), pressão intracraniana máxima (PIM), ocorrência de trombose venosa cerebral (TVC), e as modalidades de tratamento foram revisadas. PV foi graduada em discreta, moderada e grave, baseada na acuidade e no campo visual. Fatores preditivos para perda e melhora visual foram avaliados por análise de regressão linear. Resultados: Quarenta e três pacientes eram do sexo feminino. A média de idade, o IMC e a PIM (± desvio padrão) foram: 35,2 ± 12,7 anos, 32,0 ± 7,5 kg/cm2 e 41,9 ± 14,5 cmH2O, respectivamente. Sintomas visuais estavam presentes em 46 e TVC em 8 pacientes. TD (em meses) foi <1 em 21, 1-6 em 15 e >6 em 14 pacientes. Pacientes receberam tratamento clinico apenas (n=30) ou associado a tratamento cirúrgico (n=20). Na apresentação a PV era discreta em 16, moderada em 12 e grave em 22 pacientes. Vinte e oito pacientes melhoraram e 5 pioraram. PIM, TD e hipertensão arterial correlacionaram significativamente com PV grave. O melhor fator preditivo para PV grave foi o TD>6 meses (p=0,04; razão de chances 5,18). TD entre 1 e 6 meses foi o único fator significativamente associado com melhora visual após tratamento (p=0,042). Conclusões: Perda visual é comum na SPC e quando grave se mostra relacionado a atraso no diagnóstico. É usualmente permanente mas pode haver melhora visual especialmente quando a doença é diagnosticada nos primeiros 6 após o início dos sintomas. .

Knowledge and practice of Brazilian pediatricians on gastroesophageal reflux disease in infants / Conhecimento e prática de pediatras brasileiros sobre a doença do refluxo gastroesofágico em lactentes

OBJECTIVE: To assess the knowledge and practice of pediatricians about infants with physiological reflux and gastroesophageal reflux disease. METHODS: 140 pediatricians were interviewed during two scientific events in 2009 and 2010. The questions referred to two clinical cases of infants. One with symptoms of infant regurgitation (physiological reflux) and another with gastroesophageal reflux disease. RESULTS: Among 140 pediatricians, 11.4% (n=16) and 62.1% (n=87) would require investigation tests, respectively for infant regurgitation (physiological reflux) and gastroesophageal reflux disease. A series of upper gastrointestinal exams would be the first requested with a higher frequency. Medication would be prescribed by 18.6% (n=6) in the case of physiological reflux and 87.1% (n=122) in the case of gastroesophageal reflux disease. Prokinetic drugs would be prescribed more frequently than gastric acid secretion inhibitors. Sleeping position would be recommended by 94.2% (n=132) and 92.9% (n=130) of the respondents, respectively for the case of physiological reflux and gastroesophageal reflux disease; however, about half of the respondents would recommend the prone position. Only 10 (7.1%) of the pediatricians would exclude the cow's milk protein from the infants' diet. CONCLUSIONS: Approaches different from the international guidelines are often considered appropriate, especially when recommending a different position other than the supine and prescription of medication. In turn, the interviews enable us to infer the right capacity of the pediatricians to distinguish physiologic reflux and gastroesophageal reflux disease correctly. .

OBJETIVO: Avaliar o conhecimento e a prática de pediatras brasileiros na assistência ao lactente com refluxo fisiológico e doença do refluxo gastroesofágico. MÉTODOS: Foram entrevistados 140 médicos pediatras em dois eventos científicos em 2009 e 2010. As perguntas referiam-se a dois casos clínicos de lactentes, um com quadro compatível com regurgitação do lactente (refluxo fisiológico) e outro com doença do refluxo gastroesofágico. RESULTADOS: Dos 140 participantes, 11,4% (n=16) e 62,1% (n=87) solicitariam exame para lactentes, respectivamente, com refluxo fisiológico e doença do refluxo gastroesofágico. O primeiro exame solicitado com maior frequência seria a radiografia contrastada de esôfago, estômago e duodeno. Medicação seria prescrita por 18,6% (n=26) para o caso de refluxo fisiológico e 87,1% (n=122) para o caso de doença do refluxo gastroesofágico. Procinéticos seriam prescritos com maior frequência do que os redutores da secreção ácida gástrica. Prescrição de posição para dormir fez parte das recomendações de 94,2% (n=132) e 92,9% (n=130) dos entrevistados, respectivamente, para os casos de refluxo fisiológico e doença do refluxo gastroesofágico. Entretanto, cerca da metade dos entrevistados não recomendaria o decúbito dorsal. Prescrição de dieta de exclusão do leite de vaca para um lactente com quadro de doença do refluxo gastroesofágico seria feita por apenas 10 (7,1%) dos participantes. CONCLUSÕES: Condutas diferentes das diretrizes internacionais são frequentemente consideradas adequadas, especialmente quanto à recomendação de posição diferente do decúbito dorsal e prescrição de medicamentos. As respostas permitem inferir a capacidade de correta diferenciação entre refluxo fisiológico e doença do refluxo gastroesofágico. .

Evaluation of the diuretic effects of crude stem bark extraction of Zanthoxylum heitzii (Rutaceae) in Wistar rats / 中西医结合学报

<p><b>OBJECTIVE</b>Zanthoxylum heitzii is a medicinal plant widely used in central Africa for the treatment of many diseases, especially cardiovascular diseases and hypertension. The diuretic effects of crude stem bark extraction were determined and its safety in rats was evaluated.</p><p><b>METHODS</b>The diuretic effects of crude stem bark extraction of Z. heitzii 250 g ± 10 g) of both sexes. The crude stem bark extraction of Z. heitzii at the doses of 225, 300 and 375 mg/kg was administered to rats at 5 mL/kg body weight. Urine volume was determined 1, 2, 3, 4, 5, 6 and 24 h after administration of the extract. Kinetics of electrolyte elimination in response to a single oral administration dose of acute treatment was measured. The experiments were performed under the same conditions with two synthetic pharmacological diuretics considered as reference (furosemide and hydrochlorothiazide). Urinary and plasma concentrations of sodium and potassium ions were determined using flame photometry. Concentrations of creatinine, urea, glucose, albumin and electrolytes in the plasma and urine samples were evaluated using a two-way digital bidirectional spectrophotometer. The osmolarity of plasma and urine samples was measured by cytometry using an osmometer. Aldosterone was measured by radioimmunoassay.</p><p><b>RESULTS</b>The plant extract accelerated the elimination of overloaded fluid and increased urine volume and the excretion of Na+, K+ and Cl- 24 h after administration (P<0.05). The increase in elimination of Na+, K+, and Cl- induced by caused alkalinization of the urine, and showed a strong inhibitory effect on carbonic anhydrase and saluretic. These effects were mainly observed at the dose of 375 mg/kg. At the maximum diuretic response, urinary osmolarity decreased significantly (P<0.05) when compared to controls. The stability of aldosterone level, the absence of correlation with the plasma levels of Na+, and increased clearance of free water in the animals treated with indicated that increased diuresis and natriuresis were tubular in origin. No significant (P>0.05) changes were observed in the body temperature of the animals.</p><p><b>CONCLUSION</b>The significant increase in urine volume 24 h after treatment followed a dose-response pattern. The excretion of Na+, K+ and Cl- caused a decrease in urine osmolarity. The stability of aldosterone, the absence of correlation with the plasma levels of sodium, and increased clearance of free water in animals treated with aqueous extract suggest that increased diuresis and moderate natriuresis elevation were of tubular origin.</p>

Ultrastructural changes of erythrocytes in whole blood after exposure to prospective in silico-designed anticancer agents: a qualitative case study

BACKGROUND: Novel, in silico-designed anticancer compounds were synthesized in our laboratory namely, 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16). These compounds were designed to have improved bioavailability when compared to their source compound, 2-methoxyestradiol. This theoretically would be due to their increased binding affinity to carbonic anhydrase II, present in erythrocytes. Since the novel compounds under investigation are proposed to be transported within erythrocytes bound to carbonic anhydrase II, the morphological effect which they may exert on whole blood and erythrocytes is of great significance. A secondary outcome included revision of previously reported procedures for the handling of the whole blood sample. The purpose of this study was twofold. Firstly, the ultrastructural morphology of a healthy female's erythrocytes was examined via scanning electron microscopy (SEM) after exposure to the newly in silico-designed compounds. Morphology of erythrocytes following exposure to ESE-15-ol and ESE-16 for 3 minutes and 24 hours at 22°C were described with the use of SEM. The haemolytic activity of the compounds after 24 hours exposure were also determined with the ex vivo haemolysis assay. Secondly, storage conditions of the whole blood sample were investigated by determining morphological changes after a 24 hour storage period at 22°C and 37°C. RESULTS: No significant morphological changes were observed in the erythrocyte morphology after exposure to the novel anticancer compounds. Storage of the whole blood samples at 37°C for 24 hours resulted in visible morphological stress in the erythrocytes. Erythrocytes incubated at 22°C for 24 hours showed no structural deformity or distress. CONCLUSIONS: From this research the optimal temperature for ex vivo exposure of whole blood samples to ESE-15-ol and ESE-16 for 24 hours was determined to be 22°C. Data from this study revealed the potential of these compounds to be applied to ex vivo study techniques, since no damage occurred to erythrocytes ultrastructure under these conditions. As no structural changes were observed in erythrocytes exposed to ESE-15-ol and ESE-16, further ex vivo experiments will be conducted into the potential effects of these compounds on whole blood. Optimal incubation conditions up to 24 hours for whole blood were established as a secondary outcome.

Toxic Epidermal Necrolysis in a Patient with HLA-B*5901 Haplotype Caused by Topical and Oral Carbonic Anhydrase Inhibitors

No abstract available.

The Effects of Topical Carbonic Anhydrase Inhibitors on Nitric Oxide Production in Trabecular Meshwork Cells

PURPOSE: To investigate and compare the effects of topical carbonic anhydrase inhibitors on the production and expression of nitric oxide in cultured human trabecular meshwork cells (HTMC). METHODS: Primarily cultured HTMC were exposed to 0, 10, and 100 microM dorzolamide and brinzolamide using serum-deprived media for 3 days. Production of nitric oxide was assessed with Griess assay. Expressions of eNOS mRNA were assessed with RT-PCR. RESULTS: Both dorzolamide and brinzolamide increased the production of nitric oxide eNOS activity (p < 0.05). Dorzolamide had a more potent effect than brinzolamide on the production of nitric oxide and the expression of eNOS mRNA. CONCLUSIONS: Topical carbonic anhydrase inhibitors increased the production of nitric oxide, which was accompanied by increased eNOS activity. Dorzolamide had a more potent effect than brinzolamide on the production of nitric oxide and expression of eNOS mRNA in HTMC. The increased production of nitric oxide by topical carbonic anhydrase inhibitors involves mechanisms other than carbonic anhydrase inhibition.

Efectividad y seguridad de timolol combinaciones y dorzolamida combinaciones en pacientes con glaucoma de ángulo abierto, glaucoma de ángulo cerrado o presión intraocular elevada / Effectiveness and safety of timolol combinations and dorzolamide combinations in patients with open-angle glaucoma, angle-closure glaucoma or elevated intraocular pressure

Introducción: Antecedentes: Descripción de la condición de salud de interés: El glaucoma se define como una neuropatía óptica con daño estructural del nervio óptico acompañado de una disfunción visual secundaria (1). Un daño leve del nervio óptico puede ser asintomático; 50% de los pacientes en países desarrollados con glaucoma pueden no saber que padecen de dicha enfermedad (2-3) . Sin embargo, conforme la enfermedad avanza los síntomas se instauran y empeoran reduciendo la visión periférica, la sensibilidad al contraste, entre otras funciones propias de la visión, comprometiendo la realización de las actividades diarias y en última instancia, el desarrollo de ceguera. Descripción de la tecnología: El tratamiento farmacológico para el glaucoma busca disminuir la presión intraocular a un nivel que sea seguro para el paciente, disminuyendo la producción de humor acuoso o aumentando la salida del mismo del ojo, con el fin de evitar la aparición de ceguera por glaucoma. Evaluación de efectividad y seguridad: Pregunta de investigación: En pacientes con Glaucoma de Ángulo Abierto o Cerrado o con Presión Intraocular elevada, ¿es más efectivo y seguro el timolol y dorzolamida en combinaciones en comparación con brimonidina, timolol, latanoprost, acetazolamida, pilocarpina, betaxolol, tafluprost o bimatoprost para reducir la presión intraocular? La pregunta de investigación fue validada teniendo en cuenta las siguientes fuentes de información: registro sanitario INVIMA, Acuerdo 029 de 2011, guías de práctica clínica, reportes de evaluación de tecnologías, revisiones sistemáticas y narrativas de la literatura, estudios de prevalencia/incidencia y carga de enfermedad, consulta con expertos temáticos, y otros actores clave. Población: Adultos con diagnóstico de hipertensión intraocular, glaucoma de ángulo abierto o de ángulo cerrado. Tecnología de interés: \tTimolol y dorzolamida en combinaciones (Timolol con: dorzolamida, latanoprost, travoprost, bimatoprost. Dorzolamida combinado con Timolol). Conclusiones: Efectividad: en pacientes con presión intraocular o glaucoma de ángulo abierto, timolol en sus combinaciones (travoprost o latanoprost) es más efectivo que los análogos de prostaglandinas solos (latanoprost y travoprost) para la reducción de la presión intra ocular. Asimismo, la combinación de timolol con travoprost, latanoprost y dorzolamida comparado con timolol solo, es más efectiva para la reducción de la presión intraocular. Seguridad: las combinaciones de medicamentos producen más hiperemia conjuntival que el tratamiento con un solo medicamento. No hay evidencia de comparaciones directas entre los medicamentos de interés para definir diferencias respecto a seguridad. La combinación de timolol con bimatoprost fue la que más eventos adversos produjo, comparado con la monoterapia de travoprost, seguido de latanoprost. dorzolamida con timolol es más seguro en comparación con bimatoprost como monoterapia. No se encontró evidencia para otras combinaciones de timolol o dorzolamida.(AU)

Efectividad y seguridad de dorzolamida para reducción de la presión intraocular en pacientes con glaucoma de ángulo abierto, glaucoma de ángulo cerrado o presión intraocular elevada / Effectiveness and safety of dorzolamide for reduction of intraocular pressure in patients with open-angle glaucoma, angle-closure glaucoma or elevated intraocular pressure

Introducción: Antecedentes: Descripción de la condición de salud de interés: El glaucoma se define como una neuropatía óptica con daño estructural del nervio óptico acompañado de una disfunción visual secundaria (1). Un daño leve del nervio óptico puede ser asintomático; 50% de los pacientes en países desarrollados con glaucoma pueden no saber que padecen de dicha enfermedad (2-3) . Sin embargo, conforme la enfermedad avanza los síntomas se instauran y empeoran reduciendo la visión periférica, la sensibilidad al contraste, entre otras funciones propias de la visión, comprometiendo la realización de las actividades diarias y en última instancia, el desarrollo de ceguera. Descripción de la tecnología: El tratamiento farmacológico para el glaucoma busca disminuir la presión intraocular a un nivel que sea seguro para el paciente, disminuyendo la producción de humor acuoso o aumentando la salida del mismo del ojo, con el fin de evitar la aparición de ceguera por glaucoma. Dorzolamida hidrocloruro es un potente inhibidor de la anhidrasa carbónica II humana. La administración tópica en el ojo disminuye la hipertensión intraocular, ya esté o no asociada con glaucoma. La hipertensión intraocular es un factor de riesgo importante en la patogenia de la lesión del nervio óptico y de la pérdida del campo visual. Dorzolamida no produce contracción pupilar y reduce la presión intraocular sin efectos secundarios, tales como ceguera nocturna y espasmo acomodativo. Ejerce un efecto mínimo o nulo sobre la velocidad del pulso o la presión arterial. Evaluación de efectividad y seguridad: En pacientes con Glaucoma de Ángulo Abierto (GAA) o Cerrado (GAC) o con Presión Intraocular (PIO) elevada, ¿es más efectiva y segura la dorzolamida en comparación con brimonidina, timolol, latanoprost, acetazolamida, pilocarpina, betaxolol, tafluprost o bimatoprost para reducir la presión intraocular? La pregunta de investigación fue validada teniendo en cuenta las siguientes fuentes de información: registro sanitario INVIMA, Acuerdo 029 de 2011, guías de práctica clínica, reportes de evaluación de tecnologías, revisiones sistemáticas y narrativas de la literatura, estudios de prevalencia/incidencia y carga de enfermedad, consulta con expertos temáticos, y otros actores clave. Población: Adultos con diagnóstico de hipertensión intraocular, glaucoma de ángulo abierto o de ángulo cerrado. Tecnología de interés: \tDorzolamida. Metodología: Búsqueda de literatura: Se llevó a cabo una búsqueda sistemática y exhaustiva, con el objetivo de identificar evidencia científica relevante en relación con la pregunta de evaluación. Todo el proceso se acogió a los estándares de calidad internacional utilizados en revisiones sistemáticas de la literatura (11). Las búsquedas fueron llevadas a cabo por personal entrenado. Discusión: La búsqueda de la literatura no arrojó muchos resultados comparando la dorzolamida contra otros medicamentos de interés, ya que sólo dos estudios fueron identificados con la estrategia de búsqueda. Para el tratamiento de glaucoma hay varias opciones terapéuticas, enumeradas anteriormente, y por tanto puede ocurrir que no hayan comparaciones directas entre ciertos tratamientos (comparaciones cabeza a cabeza). Los resultados del meta-análisis en red presentados en este reporte dan cuenta de una efectividad similar o incluso inferior de la dorzolamida comparada contra timolol cada 12 horas. Asimismo, la dorzolamida tiene una efectividad inferior que el latanoprost, teniendo ambos un perfil de seguridad similar. Las guías de práctica clínica (3) sugieren comenzar el tratamiento en monoterapia con timolol o con latanoprost, que es el análogo de prostaglandinas que menos eventos adversos presenta; los resultados aquí presentados apoyan esta recomendación. Conclusiones: Efectividad: Dorzolamida es menos efectiva para disminuir la presión intraocular que timolol y latanoprost en pacientes con GAA o PIO. No se encontraron comparaciones contra brimonidina, acetazolamida, pilocarpina, betaxolol, tafluprost y bimatoprost. Seguridad: No hay diferencias en eventos adversos entre dorzolamida y latanoprost. . No se encontraron comparaciones contra timolol, brimonidina, acetazolamida, pilocarpina, betaxolol, tafluprost y bimatoprost.

Progress in the study of carbonic anhydrase inhibitors as potential anticancer drugs / 药学学报

Carbonic anhydrase IX (CA IX) is a tumor associated protein which is able to be a potent anticancer target, since it is highly expressed in a multitude of carcinomas, while it is present in a limited number of normal tissues. This review focuses on its role in tumor physiology, the most recent three dimensional structure features of this enzyme which has recently been elucidated. In addition, we present recent advances in the development of small inhibitors able to target CA IX for therapeutic applications.

Analysing the effect of early acetazolamide administration on patients with a high risk of permanent cerebrospinal fluid leakage

In this study, we examined the role of early acetazolamide administration in reducing the risk of cerebrospinal fluid [CSF] leakage in patients with a high risk of permanent CSF leakage. In a randomised clinical trial, 57 patients with a high risk of permanent CSF leakage [rhinorrhea, otorrhea, pneumatocele or imaging-based evidence of severe skull-base fracture] were analysed. In the experimental group, acetazolamide, at 25 mg/kg/day, was started in the first 48 hours after admission. In the control group, acetazolamide was administered after the first 48 hours at the same dose administered to the patients in the experimental group. The following factors were compared between the two groups: duration of CSF leakage, duration of hospital stay, incidence of meningitis, need for surgical intervention and need for lumbar puncture [LP] and lumbar drainage [LD]. All of the patients in the experimental group stopped having CSF leakage less than 14 days after the first day of admission, but 6 out of 21 patients [22%] in the control group continued having CSF leakage after 14 days of admission, which was a significant difference [P=0.01]. This study showed that early acetazolamide administration can prevent CSF leakage in patients with a high risk of permanent CSF leak

Topiramato, efectos en el estado ácido base y consecuencias clínicas / Topiramate: Effects on the Acid-Base Status and Clinical Consequences

En la presente revisión se analiza cómo el topiramato afecta a corto y largo plazo el estado ácido base mediante la inhibición de la anhidrasa carbónica tipo II, generando una acidosis tubular renal mixta que provoca consecuencias clínicas de importancia como nefrolitiasis, osteoporosis y retraso en el crecimiento. Dado que los tratamientos con este fármaco son crónicos, pueden prevenirse estos sucesos de diversas maneras. Se ofrecen pautas para el manejo de las distintas situaciones clínicas

This review provides an analysis of the short-and long-term impact of Topiramate on the acid-base status through the inhibition of carbonic anhydrase II, which leads to a mixed renal tubular acidosis that causes significant clinical consequences such as nephrolithiasis, osteoporosis and growth delay. Because treatments with this drug are chronic, these events may be prevented in different ways. The author offers guidelines for the management of different clinical situations