Expression of ubiquitin-specific protease 7 in lung tissue of preterm rats after hyperoxia exposure / 中国当代儿科杂志

OBJECTIVE@#To study the expression and significance of ubiquitin-specific protease 7 (USP7) and the key factors of the Wnt signaling pathway in the lung tissue of preterm rats after hyperoxia exposure.@*METHODS@#A total of 180 preterm neonatal Wistar rats were randomly divided into an air control group, an air intervention group, a hyperoxia control group, and a hyperoxia intervention group, with 45 rats in each group. Lung injury was induced by hyperoxia exposure in the hyperoxia groups. The preterm rats in the intervention groups were given intraperitoneal injection of the USP7 specific inhibitor P5091 (5 mg/kg) every day. The animals were sacrificed on days 3, 5, and 9 of the experiment to collect lung tissue specimens. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue. RT-PCR and Western blot were used to measure the mRNA and protein expression levels of USP7 and the key factors of the Wnt signaling pathway β-catenin and α-smooth muscle actin (α-SMA) in lung tissue.@*RESULTS@#The air groups had normal morphology and structure of lung tissue; on days 3 and 5, the hyperoxia control group showed obvious alveolar compression and disordered structure, with obvious inflammatory cells, erythrocyte diapedesis, and interstitial edema. On day 9, the hyperoxia control group showed alveolar structural disorder and obvious thickening of the alveolar septa. Compared with the hyperoxia control group at the corresponding time points, the hyperoxia intervention group had significantly alleviated disordered structure, inflammatory cell infiltration, and bleeding in lung tissue. At each time point, the hyperoxia groups had a significantly lower radial alveolar count (RAC) than the corresponding air groups (@*CONCLUSIONS@#Hyperoxia exposure can activate the Wnt/β-catenin signaling pathway, and USP7 may participate in hyperoxic lung injury through the Wnt/β-catenin signaling pathway. The USP7 specific inhibitor P5091 may accelerate the degradation of β-catenin by enhancing its ubiquitination, reduce lung epithelial-mesenchymal transition, and thus exert a certain protective effect against hyperoxic lung injury.

Strontium ranelate inhibits wear particle-induced aseptic loosening in mice

The imbalance between bone formation and osteolysis plays a key role in the pathogenesis of aseptic loosening. Strontium ranelate (SR) can promote bone formation and inhibit osteolysis. The aim of this study was to explore the role and mechanism of SR in aseptic loosening induced by wear particles. Twenty wild-type (WT) female C57BL/6j mice and 20 sclerostin-/- female C57BL/6j mice were used in this study. Mice were randomly divided into four groups: WT control group, WT SR group, knockout (KO) control group, and KO SR group. We found that SR enhanced the secretion of osteocalcin (0.72±0.007 in WT control group, 0.98±0.010 in WT SR group, P=0.000), Runx2 (0.34±0.005 in WT control group, 0.47±0.010 in WT SR group, P=0.000), β-catenin (1.04±0.05 in WT control group, 1.22±0.02 in WT SR group, P=0.000), and osteoprotegerin (OPG) (0.59±0.03 in WT control group, 0.90±0.02 in WT SR group, P=0.000). SR significantly decreased the level of receptor activator for nuclear factor-κB ligand (RANKL) (1.78±0.08 in WT control group, 1.37±0.06 in WT SR group, P=0.000) and improved the protein ratio of OPG/RANKL, but these effects were not observed in sclerostin-/- mice. Our findings demonstrated that SR enhanced bone formation and inhibited bone resorption in a wear particle-mediated osteolysis model in wild-type mice, and this effect relied mainly on the down-regulation of sclerostin levels to ameliorate the inhibition of the canonical Wnt pathway.

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Considering that osteoarthritis (OA) is the most prevalent joint disease worldwide, multiple pharmacological treatments have been proposed to alter the articular structure with potential benefit in the progression of the disease. The so-called disease-modifying OA drugs have been frequently investigated but conclusive findings are rare. Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects in decreasing the risk of fractures and possible effect in reducing the progression of OA. The objective of this review was to demonstrate the current panorama of knowledge on the use of SrRan in clinical and experimental models, clarifying its mechanisms of action and describing possible anti-nociceptive and anti-inflammatory effects. The systematic review was based on the PRISMA statement and included articles that are indexed in scientific databases. Fifteen studies were included: seven pre-clinical and eight clinical studies. Despite the limited number of studies, the results suggest a positive effect of SrRan in patients with OA, through changes in functional capacity and reduction of progression of morphological parameters and joint degradation, with moderate quality of evidence for those clinical outcomes. Novel studies are necessary to elucidate the molecular targets of SrRan, focusing on anti-inflammatory effects and histological changes promoted by SrRan, which seemed to reduce the progression of OA in the experimental and clinical studies.

Effects of strontium ranelate on alveolar ridge morphology augmentation / Efectos del ranelato de estroncio en el aumento del rebforde alveolar

SUMMARY: The objective of this study was to compare the Primary and Secondary stability of immediate implant placement with Alveolar Ridge Augmentation (ARA) and Strontium Ranelate (SR) as aids to enhance the stability using Resonance Frequency Analysis (RFA). Fifty eight subjects ideal for immediate implants were assigned to two groups to compare the primary and secondary stability of the implant using Alveolar Ridge Augmentation and oral strontium ranelate. They were tested for primary stability on placement of the implant and after eight weeks of placement for secondary stability. The stability was measured using resonance frequency analysis. Both the procedures showed an improvement in the stability but the Alveolar Ridge Augmentation procedure showed a significantly better primary stability (P< .03) and the secondary stability (P<.00). The means of the implant stability quotient value (ISQ) for the Alveolar ridge augmentation procedure was 74.2 for primary stability, and 83.34 for secondary stability. With the enhancement of stability with both the procedures Alveolar Ridge Augmentation proved to be a better procedure to achieve successful results of an immediately placed implant.

RESUMEN: El objetivo de este estudio fue comparar la estabilidad primaria y secundaria de la colocación inmediata del implante con el aumento de reborde alveolar (ARA) y el ranelato de estroncio (SR) como ayudas para mejorar la estabilidad mediante el análisis de frecuencia de resonancia (RFA). Cincuenta y ocho sujetos, ideales para implantes inmediatos, fueron asignados a dos grupos para comparar las estabilidades primaria y secundaria del implante usando el aumento del reborde alveolar y el ranelato de estroncio oral. Se efectuaron pruebas de estabilidad primaria en la colocación del implante, y después de ocho semanas para la estabilidad secundaria. La estabilidad se midió utilizando análisis de frecuencia de resonancia. Ambos procedimientos mostraron una mejora en la estabilidad, sin embargo el procedimiento del aumento del reborde alveolar mostró una estabilidad primaria significativamente mejor (P <0,03) que la estabilidad secundaria (P <0,00). Las medias del valor de cociente de estabilidad del implante (ISQ) para el procedimiento de aumento de reborde alveolar fueron 74,2 para la estabilidad primaria y 83,34 para la estabilidad secundaria. Se observó una mejora de la estabilidad en ambos procedimientos, el aumento del reborde alveolar demostró ser un mejor procedimiento para lograr resultados exitosos del posicionamiento de implante inmediato.

Strontium Ranelate Effect on the Repair of Bone Defects and Molecular Components of the Cortical Bone of Rats

Abstract This study was conducted to evaluate the effects of treatment with strontium ranelate (SR) on the repair of bone defects and molecular components of bones in femurs. Adult female rats (n=27) were subjected to ovariectomy (OVX) or Sham surgery. Thirty days after surgery, a defect was made in the femur and the animals were then divided into three groups: OVX, SHAM and OVX+SR. Euthanasia was performed four weeks after the bone defect surgery. Repair in bone defect was assessed by computed microtomography (μCT) and chemical composition of cortical bone was analyzed by Fourier transform infrared (FTIR) spectroscopy and energy dispersive X-ray spectroscopy (EDS). The trabecular thickness (Tb.Th) of the newly formed bone in the OVX+SR group was significantly higher than that for the OVX group. The collagen maturity in the OVX+SR group was smaller than in the other two groups. In this group, a significant increase in the amount of strontium (Sr) and a decrease in the amount of calcium (Ca) embedded to bone tissue were also observed. Systemic treatment with SR improved microarchitecture of the newly formed bone inside the defect, but decreased cross-linking of mature collagen in cortical bone.

Resumo Este estudo foi conduzido para avaliar os efeitos do tratamento com ranelato de estrôncio (RE) na reparação de defeitos ósseos e componentes moleculares de ossos nos fêmures. Ratas adultas (n = 27) foram submetidas a ovariectomia (OVX) ou cirurgia Sham. Trinta dias após a cirurgia, um defeito foi feito no fêmur e os animais foram então divididos em três grupos: OVX, SHAM e OVX+RE. A eutanásia foi realizada quatro semanas após a cirurgia de preparo do defeito ósseo. A reparação do defeito ósseo foi avaliada por microtomografia computorizada (μCT) e a composição química do osso cortical foi analisada por espectroscopia de infravermelho de transformada de Fourier (FTIR) e espectroscopia por energia dispersiva de raios X (EDS). A espessura do osso trabecular (Tb.Th) recém formado no grupo OVX+SR foi significativamente maior que a do grupo OVX. A maturidade do colágeno no grupo OVX+SR foi menor do que nos outros dois grupos. Neste grupo, observou-se também um aumento significativo na quantidade de estrôncio (Sr) e uma diminuição na quantidade de cálcio (Ca) no tecido ósseo. O tratamento sistêmico com RE melhorou a microarquitetura do osso recém formado dentro do defeito, mas diminuiu a reticulação do colágeno maduro no osso cortical.

Efectos in vivo del ranelato de estroncio sobre células progenitoras de médula ósea de ratas diabéticas / In vivo effects of strontium ranelate on bone marrow progenitor cells of diabetic rats

La diabetes mellitus (DM) crónica se asocia con reducción en el contenido mineral óseo (osteopenia y osteoporosis). El objetivo de este trabajo fue evaluar la acción del ranelato de estroncio (RaSr) administrado por vía oral a animales control y diabéticos, sobre el potencial osteogénico de células progenitoras de médula ósea (CPMO). Dieciséis ratas Wistar macho jóvenes se dividieron en dos grupos: controles (C) y diabéticas (D) con destrucción parcial de células b-pancreáticas mediante inyecciones intraperitoneales consecutivas de nicotinamida y estreptozotocina. Siete días después de la inyección, cada grupo se subdividió: sin tratamiento, o tratadas oralmente con RaSr (625 mg/kg/día) durante seis semanas, luego de lo cual los animales fueron sacrificados. Las CPMO se obtuvieron de ratas de los cuatro grupos, por lavados del canal diafisario medular (húmero o fémur o ambos) y cultivo hasta confluencia en DMEM-10% FBS. La proliferación celular se evaluó mediante el ensayo de MTT. Luego las CPMO se replaquearon e incubaron en un medio osteogénico durante 14 días (fosfatasa alcalina [FAL] y colágeno tipo 1) o 21 días (mineralización). Las CPMO del grupo C+RaSr mostraron un aumento significativo versus control en la proliferación (133%) y en la diferenciación osteogénica (colágeno 143%, FAL 168%, mineralización 117%). La DM (grupo D) disminuyó significativamente la proliferación y diferenciación osteoblástica de las CPMO. El tratamiento con RaSr (grupo D+RaSr) previno completamente estos efectos antiosteogénicos de la DM. Así, en nuestro modelo experimental in vivo, la DM disminuye el potencial osteogénico de CPMO, efecto que puede ser prevenido por un tratamiento oral con RaSr. (AU)

Chronic diabetes mellitus (DM) is associated with a reduction in bone mineral content (osteopenia and osteoporosis). The object of this study was to evaluate the in vivo effect of he anti-osteoporotic drug strontium ranelate (SrRa) administered orally to control and diabetic animals, on the osteogenic potential of bone marrow progenitor cells (BMPC). Sixteen young male Wistar rats were divided into two groups: control (C) and diabetic with partial beta-cell destruction via consecutive intra-peritoneal injections of nicotinamide and streptozotocin (D). Seven days postinjection, each group was sub-divided: without treatment, or oral treatment with SrRa (625 mg/kg/day) for six weeks, after which the animals were euthanised (groups C, C+SrRa, D, D+SrRa). BMPC were obtained from rats of all four groups by flushing of the diaphysary canal (humerus and/or femur). Adherent cells were then cultured until confluence in DMEM10% FBS. Cell proliferation was evaluated with the MTT mitogenic bioassay. BMPC were replated and incubated in an osteogenic medium for 14 days (determination of alkaline phosphatase [ALP] and type-1 collagen) or 21 days (evaluation of mineralisation). BMPC from C+SrRa rats showed a significant increase versus control in proliferation (133%) and in osteogenic differentiation (collagen 143%, ALP 168%, mineralisation 117%). Induction of diabetes (group D) significantly decreased the proliferation and osteoblastic differentiation of BMPC. Treatment of diabetic animals with SrRa (group D+SrRa) completely prevented these anti-osteogenic effects of Diabetes. Thus, in our experimental in vivo model, Diabetes decreases the osteogenic potential of BMPC, an effect that can be prevented by oral treatment with strontium ranelate. (AU)

Hemodynamic responses during and after multiple sets of stretching exercises performed with and without the Valsalva maneuver

OBJECTIVE: This study investigated the acute hemodynamic responses to multiple sets of passive stretching exercises performed with and without the Valsalva maneuver. METHODS: Fifteen healthy men aged 21 to 29 years with poor flexibility performed stretching protocols comprising 10 sets of maximal passive unilateral hip flexion, sustained for 30 seconds with equal intervals between sets. Protocols without and with the Valsalva maneuver were applied in a random counterbalanced order, separated by 48-hour intervals. Hemodynamic responses were measured by photoplethysmography pre-exercise, during the stretching sets, and post-exercise. RESULTS: The effects of stretching sets on systolic and diastolic blood pressure were cumulative until the fourth set in protocols performed with and without the Valsalva maneuver. The heart rate and rate pressure product increased in both protocols, but no additive effect was observed due to the number of sets. Hemodynamic responses were always higher when stretching was performed with the Valsalva maneuver, causing an additional elevation in the rate pressure product. CONCLUSIONS: Multiple sets of unilateral hip flexion stretching significantly increased blood pressure, heart rate, and rate pressure product values. A cumulative effect of the number of sets occurred only for systolic and diastolic blood pressure, at least in the initial sets of the stretching protocols. The performance of the Valsalva maneuver intensified all hemodynamic responses, which resulted in significant increases in cardiac work during stretching exercises. .

Analysis of Novel Anticoagulants for Atrial Fibrillation – Pharmacokinetics and Pharmacological Considerations.

Atrial Fibrillation (AF) is the most common arrhythmia. AF is a major risk factor for stoke. Warfarin has been available for more than 60 years and until recently it was the only oral anticoagulant used for the prevention of stroke. Despite the extensive studies and proven efficacy, its utility is limited by multiple factors. Warfarin interacts with a multitude of drugs and foods, has a delayed onset of action, has a narrow therapeutic range, requires routine lab monitoring and exhibits variable responses in patients. The novel agents dabigatran, rivaroxaban and apixaban have the potential to have some of the limitations of warfarin. This article will discuss the pharmacokinetic and pharmacological considerations and different characteristics of the novel anticoagulants when used for the prevention of AF.

Antifungal activity of topical microemulsion containing a thiophene derivative

Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05) embedded in a microemulsion (ME). The minimum inhibitory concentration (MIC) was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05) showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270-540 µg.mL-1) and good activity against C. neoformans (MIC = 17 µg.mL-1). Candida species were susceptible to ME-5CN05 (70-140 µg.mL-1), but C. neoformans was much more, presenting a MIC value of 2.2 µg.mL-1. The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans.

Receptores plaquetários P2Y12: importância na intervenção coronariana percutânea / P2Y12 platelet receptors: importance in percutaneous coronary intervention

As plaquetas estão envolvidas em vários processos biológicos, desde o combate a agentes infecciosos até a coordenação do controle da permeabilidade vascular e angiogênese. Entretanto, o seu principal foco de ação consiste na modulação da cascata de coagulação. A intervenção coronariana percutânea é um procedimento com alto risco trombogênico, que induz a ativação plaquetária e de monócitos, devido à lesão direta do endotélio e pelo contato de estruturas trombogênicas com o sangue, levando ao aumento da atividade inflamatória, tanto no local do dano vascular coronariano como de forma sistêmica. Os receptores plaquetários P2Y12 desempenham papel central na amplificação da agregação induzida por todos os agonistas plaquetários, como a adenosina difosfato, o colágeno, tromboxano A2, adrenalina e serotonina. Por esse motivo, têm sido o principal alvo das drogas antiplaquetárias. Apesar de atuarem no mesmo receptor, características farmacocinéticas e farmacodinâmicas distintas conferem peculiaridades a cada agente.

Apart from their role in hemostasis and thrombosis, platelets are involved in many other biological processes such as wound healing and angiogenesis. Percutaneous coronary intervention is a highly thrombogenic procedure inducing platelets and monocytes activation through endothelial trauma and contact activation by intravascular devices. Platelet P2Y12 receptor activation by adenosine diphosphate facilitates non-ADP agonist-mediated platelet aggregation, dense granule secretion, procoagulant activity, and the phosphorylation of several intraplatelet proteins, making it an ideal drug target. However, not all compounds that target the P2Y12 receptor have similar efficacy and safety profiles. Despite targeting the same receptor, the unique pharmacologic properties of each of these P2Y12 receptor-directed compounds can lead to very different clinical effects.

Impairment of locomotor activity induced by the novel N-acylhydrazone derivatives LASSBio-785 and LASSBio-786 in mice

The N-acylhydrazone (NAH) analogues N-methyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-785) and N-benzyl 2-thienylidene 3,4-benzoylhydrazine (LASSBio-786) were prepared from 2-thienylidene 3,4-methylenedioxybenzoylhydrazine (LASSBio-294). The ability of LASSBio-785 and LASSBio-786 to decrease central nervous system activity was investigated in male Swiss mice. LASSBio-785 or LASSBio-786 (30 mg/kg, ip) reduced locomotor activity from 209 ± 26 (control) to 140 ± 18 (P < 0.05) or 146 ± 15 crossings/min (P < 0.05), respectively. LASSBio-785 (15 or 30 mg/kg, iv) also reduced locomotor activity from 200 ± 15 to 116 ± 29 (P < 0.05) or 60 ± 16 crossings/min (P < 0.01), respectively. Likewise, LASSBio-786 (15 or 30 mg/kg, iv) reduced locomotor activity from 200 ± 15 to 127 ± 10 (P < 0.01) or 96 ± 14 crossings/min (P < 0.01), respectively. Pretreatment with flumazenil (20 mg/kg, ip) prevented the locomotor impairment induced by NAH analogues (15 mg/kg, iv), providing evidence that the benzodiazepine (BDZ) receptor is involved. This finding was supported by the structural similarity of NAH analogues to midazolam. However, LASSBio-785 showed weak binding to the BDZ receptor. LASSBio-785 or LASSBio-786 (30 mg/kg, ip, n = 10) increased pentobarbital-induced sleeping time from 42 ± 5 (DMSO) to 66 ± 6 (P < 0.05) or 75 ± 4 min (P < 0.05), respectively. The dose required to achieve 50% hypnosis (HD50) following iv injection of LASSBio-785 or LASSBio-786 was 15.8 or 9.5 mg/kg, respectively. These data suggest that both NAH analogues might be useful for the development of new neuroactive drugs for the treatment of insomnia or for use in conjunction with general anesthesia.

Warfarin: pharmacological profile and drug interactions with antidepressants / Varfarina: perfil farmacológico e interações medicamentosas com antidepressivos

Oral anticoagulants are among the drugs with the greatest number of drug interactions. The concomitant use of several medications is a common practice in patients with cardiovascular problems, who often also present with depression; therefore, the probability of an interaction occurring between warfarin and the antidepressants is high, and may result in increased or decreased anticoagulant activity. Since the possible interactions between these two classes of drugs have been poorly explored in literature, with a risk to the patients who use them, we reviewed the pharmacology of warfarin and its possible interactions with antidepressants. Of the antidepressants analyzed, those that showed relevant effects on the interaction with warfarin were, in decreasing order: paroxetine, venlafaxine, fluoxetine, and duloxetine.

Os anticoagulantes orais estão entre as drogas com maior número de interações medicamentosas. O uso concomitante de vários medicamentos é uma prática comum em pacientes com problemas cardiovasculares, os quais frequentemente também apresentam depressão; assim, a probabilidade de ocorrer alguma interação entre a varfarina e os antidepressivos é bem expressiva, podendo resultar em um aumento ou uma diminuição da atividade anticoagulante. Como as possíveis interações entre essas duas classes de medicamentos se mostraram pouco exploradas na literatura, com risco aos pacientes que fazem uso delas, revisamos a farmacologia da varfarina e suas possíveis interações com antidepressivos. Dos antidepressivos analisados, os que apresentaram efeitos relevantes na interação com a varfarina foram, em ordem decrescente: paroxetina, venlafaxina, fluoxetina e duloxetina.

Effect of strontium ranelate on bone remodeling

Osteoporosis is a disease in which the microarchitecture of bone tissue deteriorates, with consequent loss of bone mass. Strontium ranelate (SrR) is currently used for treatment of the condition. SrR may have a dual effect: anabolic (stimulating pre-osteoblast replication) and anti-catabolic (reducing osteoclastic activity). However, its mechanism of action has not yet been completely elucidated. The aim of this study is to evaluate the effect of SrR on bone remodeling in healthy Wistar rats. Two-month old female Wistar rats were administered SrR (2 g/L) in drinking water for 30 weeks. Oriented histological sections were prepared from lower jaw and tibia and stained with H&E, and the following histomorphometric parameters were evaluated: a) in interradicular bone: bone volume, and percentages of bone-formation, quiescent and bone-resorption surfaces; and b) in tibia: bone volume, total thickness of growth cartilage, thickness of hypertrophic cartilage zone and number of megakaryocytes. No significant difference was found in the parameters between the control animals and those treated with SrR. The results would therefore show that SrR does not alter the bone parameters studied in this experimental design.

La osteoporosis es una enfermedad caracterizada por el deterioro de la microarquitectura del tejido oseo y la consecuente perdida de masa osea. El ranelato de estroncio (RSr) es actualmente utilizado para su tratamiento ya que poseeria un efecto dual: anabolico (estimulando la replicacion de preosteoblastos) y anticatabolico (disminuyendo la actividad osteoclastica). Sin embargo, su mecanismo de accion aun no ha sido completamente dilucidado. El objetivo del presente trabajo es evaluar el efecto del RSr sobre la remodelacion osea en ratas Wistar sanas. Se utilizaron ratas Wistar hembras de dos meses de edad a las cuales se les administro RSr (2 gr/L) en el agua de bebida durante 30 semanas. Se realizaron cortes histologicos orientados de maxilar inferior y tibia coloreados con H&E y se evaluaron los siguientes parametros histomorfometricos: a) En hueso interradicular: volumen oseo, porcentaje de superficies en formacion, reposo y reabsorcion osea. b) En tibia: volumen oseo, espesor total del cartilago de crecimiento, espesor de la zona de cartilago hipertrofiado y numero de megacariocitos. No se observaron diferencias significativas en los parametros evaluados entre los animales control y los tratados con RSr. Por lo tanto, los resultados obtenidos indicarian que el RSr no altera los parametros oseos estudiados en el presente diseño experimental.

Anti-nociceptive effect of duloxetine in mouse model of diabetic neuropathic pain.

The involvement of adenosinergic pathway in the anti-nociceptive effect of duloxetine, a balanced 5-HT/NE reuptake inhibitor, was evaluated in streptozotocin induced diabetic male albino mice of Laca strain. After four weeks of single injection of streptozotocin (200 mg/kg, ip), mice were tested in the tail immersion and hot-plate assays. Cerebral adenosine levels were measured by high-performance liquid chromatography (HPLC/PDA detector). Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose, decreased body weights and reduced cerebral adenosine levels. Administration of duloxetine (5, 10 and 20 mg/kg, ip) to diabetic mice produced dose-dependent anti-nociceptive effect in both tail-immersion and hot-plate assays. Adenosine levels were also significantly and dose-dependently increased by different doses of duloxetine. The results demonstrated the involvement of adenosinergic pathway in duloxetine mediated anti-hyperalgesia in diabetic neuropathic pain.

Antidepressant behavioral effects of duloxetine and fluoxetine in the rat forced swimming test

PURPOSE: To compare the effects of the antidepressant drugs duloxetine and fluoxetine on depressive behaviors in rodents. METHODS: Eighteen male Wistar rats were given systemic injections of duloxetine, fluoxetine, or saline prior to a Forced Swimming Test (FST). Immobility and number of stops were measured. RESULTS: Rats given injections of fluoxetine displayed significantly less immobility (p = 0.02) and fewer stops than the control group (p = 0.003). Duloxetine significanlty reduced the number of stops (p = 0.003), but did not effect immobility (p = 0.48). CONCLUSION: Duloxetine and fluoxetine reduced depressive behaviors in the Forced FST. However, our findings suggest that fluoxetine is more effective than duloxetine.

OBJETIVO: Comparar o efeito antidepressivo da droga cloridrato de duloxetina com a fluoxetina. MÉTODOS: O teste do nado forçado, teste comportamental que avalia a atividade antidepressiva em ratos, foi utilizado em 18 ratos Wistar, machos adultos, divididos em três grupos iguais: duloxetina, fluoxetina e controle. RESULTADOS: Os dados do teste do nado forçado foram analisados pelo teste One-way ANOVA, Mann Whitney e Kruskall-Wallis.Houve diferença significativa (p = 0,003) entre o número de paradas dos grupos duloxetina e fluoxetina e o grupo controle. CONCLUSÃO: A duloxetina e a fluoxetina tiveram frequência de paradas similares. A fluoxetina mostrou ser mais efetiva que a duloxetina no teste do nado forçado em ratos.

Effect of topical dorzolamide on rabbit central corneal thickness

Our objective was to study the effect of dorzolamide on corneal hydration in an 18-week controlled experiment using ultrasonic pachymetry. Twenty-eight male rabbits were divided randomly into four groups. The 7 rabbits in each group received eye drops containing either 2 percent (w/v) dorzolamide or placebo in their right eye, or in their left eye. The 2 percent dorzolamide rabbits were treated every 8 h. Fellow eyes are defined as eyes which did not receive either dorzolamide or placebo. The study was blind for both the person who applied the drug and the one who performed the pachymetry. The effect of treatments is reported on the basis of the percentage of pachymetric variation compared to the measurement made before drug application. There was no significant difference (P = 0.061) in pachymetric variation between dorzolamide (-4.42 ± 11.71 percent) and placebo (2.48 ± 9.63 percent). However, there was a significant difference (P = 0.0034) in pachymetric variation between the dorzolamide fellow eyes (-7.56 ± 10.50 percent) and the placebo (-4.42 ± 11.71 percent). In conclusion, dorzolamide did not increase the corneal thickness in rabbits.

Some naturally occurring phytophototoxins for mosquito control.

Alpha-terthiophene (alpha-T) and erythrosin-B, the naturally occurring plant secondary metabolites, were tried for their phototoxic properties against Anopheles and Culex larvae under dark, ordinary tube light (1.9-2.4 w/m2) and sun light (680-840 w/m2). LC50 values of alpha-T for Anopheles larvae (4th instar) were found to be 154, 92 and 11 ppb under dark, tube light and sunlight, respectively. For Culex larvae corresponding LC50 values under different light conditions were 129, 97 and 22 ppb. Erythrosin-B under all photoregimens was found to be less toxic to larvae of both Anopheles and Culex sps. Also, the susceptibility of the mosquito species decreased with age, towards alpha-T and erythrosin-B. Cumulative effects in terms of delay in metamorphosis were also observed among survivors of such exposures. The effects of these compounds were also seen on the adults and developing unhatched embryos of a common aquatic snail (Lymnaea sps). The LC50 values of alpha-T for adults were found to be 39, 23 ppm and 77 ppb under dark, tube light and sunlight and for developing unhatched embryos the corresponding values were 620, 41 and 13 ppb. Erythrosin-B was found to be much less toxic under sunlight and dark, to both adults and embryos as compared to the toxicity of alpha-T. Potential use of such biodegradable and eco-friendly compounds of natural origin in mosquito control is discussed.

Acetylhomocysteine thiolactone protection against phosphamidon-induced alteration of regional superoxide dismutase activity in the central nervous system and its correlation with altered lipid peroxidation.

Phosphamidon intoxication (2 mg/kg body wt./day for 7 days) inhibited SOD activity, but enhanced the lipid peroxidation in various CNS regions. Administration of cithiolone (8 mg/kg body wt./day, ip for 7 days), however, elevated SOD activity and depleted lipid peroxidation. Interestingly, no significant change was observed either in SOD activity or in lipid peroxidation following simultaneous administration of phosphamidon and cithiolone.