Impact of Cadmium Mediated by Tobacco Use in Musculoskeletal Diseases.

Tobacco use has a negative impact on health due to its relationship with the development of high-mortality diseases, such as pulmonary cancer. However, the effect of cadmium (Cd), present in tobacco smoke, on the development of joint diseases has been scarcely studied. The objective of this review is to discuss the evidence regarding the mechanisms by which Cd exposure, through tobacco smoke, may lead to the development of osteoarthritis (OA), osteoporosis (OP), and rheumatoid arthritis (RA). There's evidence suggesting a string association between moderate to severe OA development and tobacco use, and that a higher blood concentration of Cd can trigger oxidative stress (OS) and inflammation, favoring cartilage loss. At the bone level, the Cd that is inhaled through tobacco smoke affects bone mineral density, resulting in OP mediated by a decrease in the antioxidant enzymes, which favors the bone resorption process. In RA, tobacco use promotes the citrullination process through Cd exposure and increases OS and inflammation. Understanding how tobacco use can increase the damage at the articular level mediated by a toxic metal, i.e., Cd, is important. Finally, we propose prevention, control, and treatment strategies for frequently disabling diseases, such as OA, OP, and RA to reduce its prevalence in the population.

Effect of cadmium on the viability on monolayer cultures of synoviocytes, chondrocytes, and Hoffa: A preliminary study.

Osteoarthritis (OA) is the gradual loss of articular cartilage and involves several tissues, such as the synovial membrane, meniscus, ligaments, and adipose tissue known as Hoffa fat pad. There are largely unexplored factors that lead to OA development, such as the impact of exposure to heavy metals like cadmium (Cd) on the viability of cells in the knee joint tissue. The objective of this report was to identify the cell type with the highest susceptibility to Cd toxicity with respect to cell viability and death. Our findings showed that a concentration as low as 3 µM cadmium chloride for 12 h affects the viability of synovial cells, and a concentration of 10 µM affects Hoffa cells. Our results suggest that Cd can affect the viability of synovial and chondral cells primarily. In contrast, Hoffa cells were less susceptible, likely because Cd favors the production of pro-inflammatory cytokines before triggering their death as part of its damage mechanism at the articular level.

Effect of cadmium on the concentration of essential metals in a human chondrocyte micromass culture.

BACKGROUND: An essential element imbalance in the joint might favor gradual degeneration of the articular cartilage. It has been reported that cadmium (Cd) plays an antagonistic role with regards to the presence of essential elements, such as zinc (Zn), iron (Fe), and manganese (Mn), which may favor the development of disabling diseases, like osteoarthritis (OA) and osteoporosis. METHODS: 3D cultures of human chondrocytes were phenotyped with the Western blot technique and structurally evaluated with histological staining. The samples were exposed to 1, 5, and 10 µM of CdCl2 for 12 h, with a non-exposed culture as control. The concentration of Cd, Fe, Mn, Zn, chromium (Cr), and nickel (Ni) was quantified through plasma mass spectrometry (ICP-MS). The data were analyzed with a Kruskal Wallis test, a Kendall's Tau test and Spearman's correlation coefficient with the Stata program, version 14. RESULTS: Our results suggest that Cd exposure affects the structure of micromass cultures and plays an antagonistic role on the concentration of essential metals, such as Zn, Ni, Fe, Mn, and Cr. CONCLUSION: Cd exposure may be a risk factor for developing joint diseases like OA, as it can interfere with cartilage absorption of other essential elements that maintain cartilage homeostasis.

Toxicity of cadmium in musculoskeletal diseases.

Epidemiological studies have reported that exposure to toxic metals like cadmium (Cd) may promote the development of musculoskeletal diseases, such as osteoporosis, rheumatoid arthritis (RA), and osteoarthritis (OA), among others. The objective of this review is to summarize the molecular mechanisms of inflammation and oxidative stress activated by Cd at the bone level, particularly in osteoporosis, RA, and OA. Cadmium can increase bone resorption, affect the activity of osteoclasts and calcium (Ca) absorption, and impair kidney function, which favors the development of osteoporosis. In the case of RA, Cd interferes with the activity of antioxidant proteins, like superoxide dismutase (SOD) and catalase (CAT). It also promotes an inflammatory state, inducing the process of citrullination, which affects the proteins of immune response. On the other hand, accumulation of Cd in the tissues and blood of smokers has been related to the development of some musculoskeletal diseases. Therefore, knowing the negative impact of Cd toxicity at the articular level can help understand the damage mechanisms it produces, leading to the development of such diseases.

Un lactante con neumatosis intestinal y neumoperitoneo: la difícil decisión de no intervenir / An infant with intestinal pneumatosis and pneumoperitoneum: the difficult decision not to intervene

El neumoperitoneo en niños puede deberse a causas que no requieran cirugía urgente, como maniobras de reanimación cardiopulmonar, patología respiratoria grave o ventilación mecánica. Intervenir en estos casos podría, incluso, empeorar el pronóstico. Presentamos el caso clínico de un lactante varón, exprematuro, con antecedente al nacer de enterocolitis necrotizante y perforación ileal, que precisó laparotomía y resección intestinal en dos ocasiones y que desarrolló un microcolon por desuso secundario. A los seis meses, tras iniciar alimentación oral exclusiva, presentó distensión abdominal con extensa neumatosis intestinal y neumoperitoneo en las radiografías. Su aspecto era bueno con tránsito intestinal conservado y ausencia de peritonitis. El paciente se mantuvo a dieta absoluta con antibioterapia endovenosa, sondaje nasogástrico y nutrición parenteral. La evolución fue favorable, reiniciando la alimentación oral a los siete días del ingreso. La existencia de un neumoperitoneo no siempre obliga a realizar una laparotomía, y la valoración global del enfermo por un equipo multidisciplinar puede evitar tratamientos agresivos innecesarios

Pneumoperitoneum in children may be due to causes that do not require urgent surgery (cardiopulmonary resuscitation manoeuvres, severe respiratory pathology or mechanical ventilation). Surgery in these cases could even worsen the prognosis. We present the case of a male infant, ex-preterm, with a history of necrotizing enterocolitis and ileal perforation at birth, requiring laparotomy and intestinal resection on two occasions and developing a secondary microcolon, due to disuse. At six months, after transitioning to full oral feeding, he presented abdominal distension with extensive intestinal pneumatosis and pneumoperitoneum on radiographs. His general appearance was good with normal intestinal transit and no peritonitis. The patient remained fasting with intravenous antibiotics, nasogastric decompression and parenteral nutrition. The evolution was favourable with oral feeding restarting on the seventh day of admission. The existence of pneumoperitoneum does not always require a laparotomy and global assessment of the patient by an interdisciplinary health team may avoid unnecessary aggressive treatments

[An infant with intestinal pneumatosis and pneumoperitoneum: the difficult decision not to intervene]. / Un lactante con neumatosis intestinal y neumoperitoneo: la difícil decisión de no intervenir.

Pneumoperitoneum in children may be due to causes that do not require urgent surgery (cardiopulmonary resuscitation manoeuvres, severe respiratory pathology or mechanical ventilation). Surgery in these cases could even worsen the prognosis. We present the case of a male infant, ex-preterm, with a history of necrotizing enterocolitis and ileal perforation at birth, requiring laparotomy and intestinal resection on two occasions and developing a secondary microcolon, due to disuse. At six months, after transitioning to full oral feeding, he presented abdominal distension with extensive intestinal pneumatosis and pneumoperitoneum on radiographs. His general appearance was good with normal intestinal transit and no peritonitis. The patient remained fasting with intravenous antibiotics, nasogastric decompression and parenteral nutrition. The evolution was favourable with oral feeding restarting on the seventh day of admission. The existence of pneumoperitoneum does not always require a laparotomy and global assessment of the patient by an interdisciplinary health team may avoid unnecessary aggressive treatments.

Hypoxia-Inducible Factors (HIFs) in the articular cartilage: a systematic review.

Osteoarthritis (OA) is the most common joint disease, and in recent years has become a major public health problem. The hallmark of OA is cartilage destruction with local commitment of subchondral bone and the synovial membrane. Hypoxia-inducible factors (HIFs) are transcriptional factors and key regulators of the cellular response to hypoxia. To date, three members of the human HIF-α protein family have been described: HIF-1α, HIF-2α, and HIF-3α. HIF-1α plays an essential role in the articular cartilage (a hypoxic tissue), as it has a protective effect in the maintenance of the articular cartilage matrix, HIF-2α has a harmful effect on the articular cartilage matrix, and HIF-3α acts as a negative regulator of HIF-1α and HIF-2α. Due to the recent growing interest in the role of HIFs in rheumatic diseases, we focused this review on the potential role of these key regulators in articular cartilage maintenance as the central axis in OA development.

Identification of the Female Sex Pheromone of the Leafroller Proeulia triquetra Obraztsov (Lepidoptera: Tortricidae).

Proeulia triquetra Obraztsov (Lepidoptera: Tortricidae) is an occasional pest in fruit orchards in central-southern Chile. In order to develop species-specific lures for detection and monitoring of this species, we identified the female-produced sex pheromone. (Z)-11-Tetradecenyl acetate (Z11-14:OAc), (E)-9-dodecenyl acetate (E9-12:OAc), and (E)-11-Tetradecenyl acetate (E11-14:OAc) were identified as biologically active compounds present in female pheromone glands by solvent extraction of the gland and analysis of the extracts by gas chromatography-electroantennographic detection and gas chromatography-mass spectrometry. In field tests, lures baited with synthetic Z11-14:OAc and E9-12:OAc in a 10:1 ratio were highly attractive to males of the species.

The antioxidant activity of soursop decreases the expression of a member of the NADPH oxidase family.

Cellular oxidative stress produced by an increase in free radicals is one of the factors that promote the development of chronic degenerative diseases; therefore, consuming natural antioxidants helps minimize their negative effects. This study evaluated the cytotoxicity of the soursop extract (Annona muricata), its cytoprotective capacity against oxidative stress induced by hydrogen peroxide, the inhibitory potential of reactive oxygen species (ROS), the molecular mechanism of its antioxidant action, and its capacity to repair cellular damage in the fibroblast cell line. The soursop extract proved not to be cytotoxic in fibroblast cultures and showed cytoprotective capacity against hydrogen peroxide-induced stress; in cell culture it reduced the generation of ROS significantly by inhibiting a sub-unit of the NADPH oxidase enzyme (p47phox). The soursop extract can prevent damage caused by cellular oxidants.

Hiperinsulinimso neonatal por nueva mutación del gen ABBCC8 con evolución hacia diabetes hipoinsulínica / Neonatal hyperinsulinism due to new mutation of ABCCS gene with evolution towards hypoinsulinemic diabetes

Recientemente se han descrito mutaciones activadoras de los genes ABCC8 y KCNJ11 causantes de hiperinsulinismo hipoglucémico seguido del desarrollo de una diabetes hipoinsulínica posterior. Se presenta un caso de hiperinsulinismo congénito neonatal por nueva mutación el gen ABCC8 con evolución hacia una diabetes hipoinsulínica al cabo de cuatro caos de evolución. Se trata de una recién nacida macrosómica afecta de hiperinsulinismo con una expresión clínica importante ya que inicialmente presentaba hipoglucemias e hiperinsulinemias severas con buena respuesta al diazóxido. Posteriormente fue estabilizándose la situación metabólica, llegando a retirarse la medicación sin apenas recaídas importantes. A continuación y coincidiendo con procesos infecciosos intercurrentes, se apreciaba tendencia a descender las glucemias sin llegar a presentar hipoglucemias e hiperinsulinemias francas y sin cetosis, que no respondieron a la medicación. Finalmente, a los cinco años de edad aparece una intolerancia a la glucosa con hiperglucemias postprandiales y una sobrecarga oral de glucosa patológica indicativa de una evolución a diabetes mellitus hipoinsulínica. Se detectó la mutación Thr1515Ala en heterocigosis en el exón 37 del gen ABCC8 responsable de la codificación de la proteína SUR1 que no hemos encontrado descrita en la literatura revisada. Se discute el posible mecanismo por la cual se pasa de un estado de hiperinsulinismo hipoglucémico a hipoinsulinismo o diabetes hipoinsulínica (AU)

The have been described recently activating mutations in ABCC8 and KCNJ11 genes that are related wyth hypoglycemic hyperinsulinism that subsequently change to hypoinsulinemic diabetes. We present a case of congenital neonatal hyperinsulinism caused by a new mutation in ABCC8 gene that changed to a hypoinsulinemic diabetes after 4 years of evolution. A macrosomic female newborn with severe hypoglycaemia and hyperinsulinemia with good response to diazoxide was followed in our Unit. Subsequently the patient remains compensated and the medication could be discontinued without symptoms of relapses of hypoglycaemia. Along the period of evolution and when the patient suffered intercurrent infectious episodes she showed tendency to present with low glycemia but without of documented hypoglycaemia, hyperinsulinemia or ketosis that did not respond to medication. When she was 5 years old the patient developed glucose intolerance with postprandial hyperglycaemia nad with an oral glucose tolerance curve compatible with hypoinsulinemic diabetes mellitus. Genetic analysis showed Thr1515Ala mutation in heterozygosis in exon 37 of the ABCC8 gene responsible of coding SUR1 protein that has not been previously described. The possible mechanisms involved in the modification of the clinical phenotype from an state of hyperinsulinemic hypoglicaemia to a state of hypoinsulinemia and diabetes are discussed (AU)

Autoevaluación del cumplimiento del protocolo de manejo de la ataxia aguda en urgencias / Self-assessment of compliance to the protocol for the management of acute ataxia in emergencies

No disponible

Distrofia miotónica. Nuestra experiencia de 18 años en consulta de Neuropediatría / Myotonic dystrophy. 18 years experience in a neuropaediatric clinic

Introducción: La distrofia miotónica es una enfermedad multisistémica autosómica dominante de expresividad variable. Se revisa nuestra experiencia de 18 años en pacientes afectados. Resultados: Se han identificado 11 pacientes confirmados con el estudio genético molecular: 2 fallecieron, 5 siguen en control, a 2 se los sigue en otro centro y 3 abandonaron el control. Tres son familiares entre sí. Iniciaron en el período neonatal 7 niños con hipotonía, 4 de ellos con sufrimiento fetal añadido. Un niño se diagnosticó a los 3 meses por el padre afectado. Una niña consultó a los 10 años por agarrotamientos de las manos desde hacía años, un niño consultó a los 5 años con posturas anómalas de las manos y un niño consultó a los 4 años por retraso psicomotor. Alteraciones asociadas: 7 niños con retraso psicomotor, 2 casos de cataratas, un caso de diabetes de tipo 1, 3 casos de hipercolesterolemia, un sarcoma de pared abdominal, un caso de fractura de fémur y cadera, 2 casos de comunicación interauricular. El diagnóstico se realizó en 5 casos por la clínica o el fenotipo de madre y niño, en 3 casos tras diagnóstico familiar y en los 3 casos no congénitos sintomáticos exclusivamente por la clínica del niño. Discusión: La distrofia miotónica es poco frecuente en nuestra experiencia; más frecuentes son las formas congénitas, que asocian con frecuencia sufrimiento perinatal. La genética permite identificar o excluir el proceso. Debe realizarse ante recién nacidos hipotónicos de causa no aclarada y plantearse en niños ante alteraciones motrices en los dedos y las manos no fácilmente explicables (AU)

Introduction: Myotonic dystrophy is a highly variable autosomic dominant inherited multisystemic disease. We review our 18 years experience with patients suffering from this disease. Results: Eleven patients were identified following a molecular genetic study: 2 patients died, 5 are still under control, 2 are being controlled in another Centre, and 3 dropped out. Three of them were relatives. Seven newborns started with hypotonic symptoms in the neonatal period, with hypotonic symptoms, of which 4 had foetal suffering. One child was diagnosed at age of 3 due to her father being affected. One girl was seen at age of 10 due to stiffness and tightening of her hands for years. One boy, aged 5, was examined due to abnormal hands posture, and a 4 year old child due to psychomotor delay. Associated disorders: 7 children with psychomotor delay, 2 cases of cataracts, 1 case of diabetes type I, 3 cases of hypercholesterolemia, 1 abdominal sarcoma, 1 case of femur and hip fracture, 2 cases of interatrial communication. The diagnostic was made in 5 cases by a clinic due to mother-son relation phenotype, in 3 cases after the family diagnosis and in another 3 cases non-congenital symptoms exclusively in the child's clinic. Discussion: In our experience, myotonic dystrophy is uncommon; it is often congenital, and is associated with perinatal suffering. Genetics can identify or exclude the process. This must be done on newborns who are hypotonic for an unknown reason. It should be suspected in a child who presents with motor abnormalities in the fingers and hands (AU)

[Myotonic dystrophy. 18 years experience in a neuropaediatric clinic]. / Distrofia miotónica. Nuestra experiencia de 18 años en consulta de Neuropediatría.

INTRODUCTION: Myotonic dystrophy is a highly variable autosomic dominant inherited multisystemic disease. We review our 18 years experience with patients suffering from this disease. RESULTS: Eleven patients were identified following a molecular genetic study: 2 patients died, 5 are still under control, 2 are being controlled in another Centre, and 3 dropped out. Three of them were relatives. Seven newborns started with hypotonic symptoms in the neonatal period, with hypotonic symptoms, of which 4 had foetal suffering. One child was diagnosed at age of 3 due to her father being affected. One girl was seen at age of 10 due to stiffness and tightening of her hands for years. One boy, aged 5, was examined due to abnormal hands posture, and a 4 year old child due to psychomotor delay. Associated disorders: 7 children with psychomotor delay, 2 cases of cataracts, 1 case of diabetes type I, 3 cases of hypercholesterolemia, 1 abdominal sarcoma, 1 case of femur and hip fracture, 2 cases of interatrial communication. The diagnostic was made in 5 cases by a clinic due to mother-son relation phenotype, in 3 cases after the family diagnosis and in another 3 cases non-congenital symptoms exclusively in the child's clinic. DISCUSSION: In our experience, myotonic dystrophy is uncommon; it is often congenital, and is associated with perinatal suffering. Genetics can identify or exclude the process. This must be done on newborns who are hypotonic for an unknown reason. It should be suspected in a child who presents with motor abnormalities in the fingers and hands.

Citomegalovirus congénito neonatal. Comunicación de un caso y revisión / Neonatal congenital cytomegalovirus. Case report and

El citomegalovirus congénito es la etiología más frecuente de infección congénita viral y la principal causa de deficiencia neurosensorial adquirida intraútero. La infección derivada de una primoinfección materna tiene consecuencias más graves que las recurrentes en cuanto a la tasa de transmisión vertical, gravedad del cuadro clínico y secuelas a largo plazo. Se comunica una nueva observación de citomegalovirus congénito neonatal, en la que el diagnóstico se sospechó ante la presencia de un retraso de crecimiento intrauterino armónico, con clínica neurológica y alteraciones neurorradiológicas características, y se revisan los principales aspectos clínicos y epidemiológicos de la afección (AU)

Title: Neonatal congenital cytomegalovirus. Case report and review Summary. Congenital cytomegalovirus is the most frequent congenital viral infection etiology and the main cause of acquired intrauterine neurosensorial failure. The infection derived from a maternal primo-infection has more serious consequences than the recurrent ones as regards to the vertical transmission rate, severity of the clinical case and long-term after effects. A new observation of neonatal congenital cytomegalovirus is reported, whose diagnosis was suspected before the presence of harmonic intrauterine growth retardation, similar to the neurological clinic and characteristic neuroradiologic alterations. The main clinical and epidemiologic aspects of the infection are reviewed (AU)

Effects of lead on the human erythrocyte membrane and molecular models.

Lead has no biological function; however, low, and particularly, high levels of exposure have a number of negative consequences for human health. Despite the number of reports about lead toxicity, very little information has been obtained regarding its effects on cell membranes. For this reason, the structural effects of lead on the human erythrocyte membranes were investigated. This aim was attained by making lead ions interact with intact erythrocytes, isolated unsealed erythrocyte membranes (IUM) and molecular models. The latter consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representing phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane. The results, obtained by electron microscopy, fluorescence spectroscopy and X-ray diffraction, indicated that (a) lead particles adhered to the external and internal surfaces of the human erythrocyte membrane; (b) lead ions disturbed the lamellar organization of IUM and DMPC large unilamellar vesicles (LUV) and (c) induced considerable molecular disorder in both lipid multilayers, the effects being much more pronounced in DMPC.

Sexual orientation and HIV infection prevalence among young Latino injection drug users in Harlem.

Among injection drug users (IDUs), those at highest risk for HIV infection include Latinos, young women, and young men who have sex with men (homosexual men). We examined how HIV infection prevalence is affected by gender and sexual orientation among young Latino IDUs in New York City. We used baseline data from a cohort study of young (18-30 years) IDUs in Harlem, New York City, conducted from 1997 through 1999. Participants were asked about drug use and sexual behaviors, and blood was taken for HIV, hepatitis B, and hepatitis C viral antibody testing. Of 156 participants who self-identified as Latino, 145 (94%) were Puerto Rican. Overall, 101 (65%) were heterosexual men, 11 (7%) were men who have sex with men (MSM), 32 (20%) were heterosexual women, and 12 (8%) were women who have sex with women (WSW). Of the whole cohort, 17 (11%) were HIV positive. HIV infection rates were higher among WSW (42%, p < 0.05), heterosexual women (16%, p < 0.05), and homosexual men (18%, p = 0.09) than heterosexual men (5%). Compared with heterosexual men, homosexual men were significantly (p < 0.05) more likely to have received money or drugs for sex (64% versus 33%), and WSW were significantly more likely to have had unprotected sex with an IDU 5 years or more older (50% versus 16%). Multivariate analysis showed being a WSW (adjusted odds ratio [AOR] = 8.68, 95% confidence interval [CI] 1.78-42.26) and having unprotected sex with an older IDU (AOR = 7.01, 95% CI 2.23-21.96) to be associated with HIV infection. Sexual transmission may account for many HIV infections among young Latino IDUs. The high prevalence of HIV infection among WSW may, in part, be due to their having unprotected sex with older men, but studies with larger sample sizes are needed to confirm this.

Chronobiological variations in the convulsive effect of monosodium L-glutamate when administered to adult rats.

Monosodium L-glutamate (MSG) when administered intraperitoneally (i.p.) to rodents induces convulsions and has been used as a model to study various aspects of status epilepticus of multifocal origin. There are circadian variations of susceptibility to convulsions induced by various factors in some animal species. The aim of this work was to learn whether the convulsive effect of MSG in rats would vary when the drug is given at different times of the day. Three subgroups of Wistar rats were given i.p. 5 mg/g MSG at 07:00, 15:00 and 23:00 h, whereas two groups of rats divided into three subgroups of five animals each were used as controls, also being injected at 07:00, 15:00 and 23:00 h. One group was injected with NaCI solution, equimolar to that of MSG (eqNaCI); the other was injected with physiological saline solution (PSS) in proportional volumes to those of the experimental group. Motor behavior was recorded for 4 h following injections in the three groups of animals. Neither signs of brain hyperexcitability, nor convulsions appeared in animals injected with PSS or eqNaCl. With MSG, no variations were seen in the latency period when data from the three subgroups studied were compared among them. Duration of convulsive period when rats were injected at 07:00 h was shorter than that seen at 15:00 and 23:00 h. No significant variations were seen in total number of convulsive episodes in the three subgroups, while the number of seizures per hour and their intensity were significantly greater when animals were injected at 07:00 h than those seen when rats were studied at 15:00 and 23:00 h. Nearly 70% of animals injected at 07:00 h died in status epilepticus, whereas no deaths were recorded in animals injected at 15:00 and 23:00 h. Results could be explained in terms of variations of physiological processes at both the brain and extracerebral tissues involved in MSG metabolism and cerebral excitability, related to circadian rhythms.

Converging and diverging beliefs about arthritis: Caucasian patients, Spanish speaking patients, and physicians.

Ninety-eight Caucasian patients, 46 Spanish speaking patients, and 50 physicians (mainly rheumatologists) took part in surveys of salient beliefs about arthritis and its treatment. The beliefs of Caucasian patients and those of physicians were similar. However, beliefs of physicians about patients' beliefs and actual patient beliefs diverged as did the beliefs of Caucasian and Spanish speaking patients. These results suggest that arthritis education and treatment should be based on patients' perceptions rather than on physicians' beliefs about patients' perceptions.