Molecular Mechanisms Involved in Hypoxia-Induced Alterations in Bone Remodeling.

Bone is crucial for the support of muscles and the protection of vital organs, and as a reservoir of calcium and phosphorus. Bone is one of the most metabolically active tissues and is continuously renewed to adapt to the changes required for healthy functioning. To maintain normal cellular and physiological bone functions sufficient oxygen is required, as evidence has shown that hypoxia may influence bone health. In this scenario, this review aimed to analyze the molecular mechanisms involved in hypoxia-induced bone remodeling alterations and their possible clinical consequences. Hypoxia has been associated with reduced bone formation and reduced osteoblast matrix mineralization due to the hypoxia environment inhibiting osteoblast differentiation. A hypoxic environment is involved with increased osteoclastogenesis and increased bone resorptive capacity of the osteoclasts. Clinical studies, although with contradictory results, have shown that hypoxia can modify bone remodeling.

Chemical compounds causing severe acute toxicity in heavy liquids used for intraocular surgery.

Perfluorocarbon liquids (PFCLs) have been considered safe for intraocular manipulation of the retina, but since 2013 many cases of acute eye toxicity cousing blindness have been reported in various countries when using various commercial PFCLs. All these PFCLs were CE marked (Conformité Européenne), which meant they had been subjected to evaluation complying with the International Organization for Standardization (ISO) guidelines. These dramatic events raised questions about the safety of PFCLs and the validity of some cytotoxicity tests performed under ISO guidelines. Samples from toxic batches were analyzed by gas chromatography-mass spectrometry combined with Raman and infrared spectrometry. Perfluorooctanoic acid, dodecafluoro-1-heptanol, ethylbenzene and tributyltin bromide were identified and evaluated by a direct contact cytotoxicity test using ARPE-19 cell line, patented by our group (EP 3467118 A1). Perfluorooctanoic acid at a concentration of >0.06 mM and tributyltin bromide at a concentration of ≥0.016 mM were shown to be toxic, whereas the concentration found in the toxic samples reached 0.48 mM, and 0.111 mM, respectively. These finding emphasized the idea that determination of partially fluorinated compounds are not enough to guarantee the safety of these medical devices.

Acute retinal toxicity associated with a mixture of perfluorooctane and perfluorohexyloctane: failure of another indirect cytotoxicity analysis.

AIMS: To report new information related to acute retinal toxicity of Bio Octane Plus, a mixture of 90% perfluorooctane (PFO) and 10% perfluorohexyloctane. METHODS: This retrospective, descriptive case series reports the occurrence of acute retinal toxicity after vitreoretinal surgery in which Bio Octane Plus (batch number 1605148) was used as an endotamponade. Cytotoxicity biocompatibility tests and chemical analyses by Fourier-transformed infrared (FTIR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) of the presumed toxic product were performed. RESULTS: Four patients presented with acute severe visual loss after uneventful ocular surgery assisted by Bio Octane Plus (batch number 1605148) as endotamponade. Patients experienced extensive retinal vascular occlusion leading to retinal and optic nerve atrophy. The viability of ARPE-19 cells directly exposed to the suspect batch for 30 min was 0%. The agarose overlay method used by the manufacturer according to European Union regulations and International Organization for Standardization (ISO) International Standards failed to detect toxicity. FTIR spectroscopy showed small differences between the non-toxic and toxic batches. GC-MS analysis showed the presence of bromotributyl stannane (whose toxicity was demonstrated in the dose-response curve) only in the toxic batch of Bio Octane Plus. CONCLUSION: This is the third report of retinotoxicity due to PFO in 4 years. The clinical profiles may be missed as they resemble other postsurgical complications; therefore, more cases worldwide could have gone unreported. Protocols to determine cytotoxicity of intraocular medical devices and approved by the ISO International Standards based on indirect methods have failed and should be revised to ensure safety.

ACUTE RETINAL DAMAGE AFTER USING A TOXIC PERFLUORO-OCTANE FOR VITREO-RETINAL SURGERY.

PURPOSE: To describe a series of retinal acute toxicity cases with severe visual loss after intraocular use of a toxic perfluoro-octane (PFO). The clinical presentation is described, and the likely causes are analyzed. New biological methods for testing safety of intraocular medical devices are proposed. METHODS: Information regarding a series of eyes suffering acute severe events after intraocular use of a toxic PFO was analyzed. Four types of spectroscopy, nuclear magnetic resonance, and chromatography were used to identify the potential PFO contaminants. Cultures of human retinal pigment epithelial cells (ARPE-19) and porcine neuroretina were used to quantify the toxicity of the suspect PFO lots. RESULTS: Of 117 cases of intraocular toxicity, 96 were considered clearly related to the use of PFO. Fifty-three cases had no light perception, and 97 had no measurable visual acuity. Retinal necrosis (n = 38) and vascular occlusion (n = 33) were the most characteristic findings. Two hydroxyl compounds, perfluorooctanoic acid and dodecafluoro-1-heptanol, and benzene derivatives were identified as the suspected toxic agents. While existing toxicity testing failed, we proposed new tests that demonstrated clear toxicity. CONCLUSION: Protocols to determine cytotoxicity of intraocular medical devices should be revised to assure safety. Acute toxic events should be reported to health authorities and scientific media.

Ghrelin and bone mass in postmenopausal hypertensive women.

BACKGROUND: Ghrelin, a recently discovered peptide mainly secreted by the stomach, has an orexigenic effect which stimulates secretion of the growth hormone. It also has vasodilator effects which reduce blood pressure and stimulate in vitro, bone formation. OBJECTIVES: To evaluate the effect of ghrelin on bone mass and bone remodeling markers in postmenopausal hypertensive women. MATERIAL AND METHODS: 25 postmenopausal hypertensive women, light to moderate based on the JNC-VII criteria, were studied. They had a mean age of 58 +/- 8 years, a body mass index of 28 +/- 6 and a hypertension development time of 65 +/- 84 months. Osteocalcin, PTHi, 25-vitamin D, ghrelin in serum and deoxypiridinoline in urine were determined in all patients. A lumbar spine densitometer was made (DXP Lunar, Madison, Wisc., USA). RESULTS: Diminished levels of ghrelin were observed in the osteoporotic group (40 +/- 19 vs. 78 +/- 40, p = 0.027). When the patients were separated according to ghrelin tertiles, a greater bone mass was observed in the upper tertiles, which was associated with a decrease in the urinary deoxypiridinoline. When the total population was analyzed, no relation between the ghrelin and bone mass was found, nor with any of the parameters of calcium metabolism. Only a statistically significant relation between ghrelin and deoxypiridinoline was observed (r = -0.428, p = 0.026). CONCLUSIONS: In postmenopausal hypertensive women, ghrelin may produce a protecting effect over bone mass through an anticatabolic mechanism manifested by a decrease of bone resorption.

Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease.

Vitamin D deficiency is a risk factor for osteoporosis and other chronic diseases, including type 1 diabetes, hypertension, metabolic syndrome, and ischemic heart disease. Cholesterol and vitamin D share the 7-dehydrocholesterol metabolic pathway. This study evaluated the possible effect of atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Eighty-three patients (52 men and 31 women) with an acute coronary syndrome (75 with acute myocardial infarction and 8 with unstable angina) were included. After diagnosis, patients received atorvastatin as secondary prevention. Serum vitamin D was measured by high-performance liquid chromatography at baseline and at 12 months. Atorvastatin treatment produced a statistically significant decrease in cholesterol and triglyceride levels and an increase in vitamin D levels (41+/-19 vs 47+/-19 nmol/L, p=0.003). Vitamin D deficiency was decreased by 75% to 57% at 12 months. In conclusion, atorvastatin increases vitamin D levels. This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels.

Effect of beta-blockers on bone mass and biomechanical parameters of the femoral neck in males with acute myocardial infarction.

OBJECTIVES: Evaluate the effect of cardioselective beta-blockers on bone mass and biomechanical properties of the femoral neck in males with acute myocardial infarction. METHODS: Forty males with acute myocardial infarction were studied during one year. Seventy-five percent of the patients (30 patients) were treated with cardioselective beta-blockers and 10 were not similarly treated. A hip densitometry was performed upon release and one year later. The BMD was measured in the femoral neck and in biomechanical elements obtained by DXA. RESULTS: Both groups had similar clinical conditions at the beginning of the study and after a one-year follow-up. No differences in the BMD (0.934+/-0.12 vs. 0.921+/-0.14) were observed in the group without beta-blockers or in the group with beta-blockers (0.980+/-0.12 vs. 0.977+/-0.12). No differences were observed in the measured structural parameters. CONCLUSION: The cardioselective beta-blockers do not modify bone mass or the structural bone parameters in males with acute myocardial infarction.

Calcium-sensing receptor gene A986S polymorphism and bone mass in hypertensive women.

BACKGROUND: The function of the calcium-sensing receptor (CaSR) is to maintain serum calcium concentration within a narrow physiological range. Two types of mutations have been described: activating that causes hypocalcemia and inactivating, which leads to hypercalcemia. The objective was to assess the effect of CaSR gene A986S polymorphism on the lumbar spine bone mass, calcium metabolism parameters and markers of bone remodeling in hypertensive women. METHODS: The study included 48 patients (mean age 59 +/- 10 years) with mild-to-moderate hypertension, according to JNC VI and who did not present any associated diseases. We determined the following in all patients: Ca, P, Mg, PTHi, 25-vitamin D, 1,25-vitamin D, osteocalcin, deoxypyridinoline in urine, 24-h urine calcium. A bone densitometry of the lumbar spine was also performed. CaSR gene A986S polymorphism was also studied in all patients by PCR. RESULTS: Genotype frequency was 69% for AA, 27% for AS and 4% for SS, with a prevalence of 82% for allele A and 18% for allele S. Patients with a lack of allele S had lower levels of p (3.5 +/- 0.5 vs. 4 +/- 0.4, p = .034). No differences in calcium plasma levels, urinary calcium excretion and bone mass were observed. CONCLUSIONS: We found no clinical significance in the parameters studied of the CaSR gene A986S polymorphism in hypertensive women.

National multicentre study of acute intoxication in emergency departments of Spain.

OBJECTIVE: No studies have been published on global acute intoxication in Spanish emergency departments. We therefore designed a multicentre study to identify the epidemiology and management of intoxicated patients in Spain. METHODS: We prospectively recorded cases from 14 emergency departments during 14 randomized days between February and April 2000. We included all age groups and all kinds of acute intoxication patients (including alcohol), except food-related cases, inert foreign bodies and deaths before arrival at the emergency department. Phone calls to poison control centres and inpatients were not followed. RESULTS: A total of 419 cases were recorded, 0.66% of emergency department visits. The incidence of intoxication was higher at weekends and on Mondays (P<0.001). The mean age was 33 years (STD+/-18.10); males represented 56%, and 34.2% of patients arrived at the emergency department within the first 2 h. A total of 80% of patients were treated as outpatients, 3.7% were admitted to the intensive care unit, 6.7% were hospitalized, and 0.2% died. DISCUSSION: We recorded a slightly lower incidence than other European countries with the same epidemiological profile, except for a low incidence of acetaminophen cases. If we apply the European Association of Poisons Centres and Clinical Toxicologists gastric lavage criteria, there were an important number of unnecessary gut decontamination techniques in drug poisoning. Most patients were treated in emergency departments, without hospital admission.

Effect of quinapril, quinapril-hydrochlorothiazide, and enalapril on the bone mass of hypertensive subjects: relationship with angiotensin converting enzyme polymorphisms.

BACKGROUND: Many alterations in extracellular metabolism of calcium have been associated to hypertension, but the number of studies relating this disease with osteoporosis is extremely low. This study clarifies the therapeutic effect of three treatments-quinapril, quinapril + hydrochlorothiazide (HCTZ), enalapril-on bone remodeling markers, bone mineral density (BMD) in hypertensive patients, and relationship with angiotensin converting enzyme (ACE) polymorphism. METHODS: This open, prospective study included 134 patients with low-to-moderate hypertension and stable BMD according to Joint National Committee criteria and 96 patients completed the study. After a washout period, patients were randomized to one of the three treatments, which they received for 1 year. Analyses of blood and urine samples and densitometric studies on lumbar spine were performed. RESULTS: Calcium and 25-hydroxyvitamin D levels increased (9.5 +/-0.3 and 9.6 +/-0.3 mg/dL, P =.01 and 46 +/-22 and 58 +/-22 nmol/L, P =.026, respectively) in the quinapril-treated group and calcium levels increased (9.4 +/-0.6 and 9.8 +/-0.4 mg/dL, P =.001) in the quinapril-HCTZ-treated group. The 1, 25-dihydroxyvitamin D levels, calciuria, and calcium/creatinine ratio decreased (64 +/-23 and 43 +/-16 nmol/L, P =.0001;209 +/-93 and 161 +/-93 mg/24 h, P =.0022;0.21 +/-0.09 and 0.17 +/-0.11, P =.04, respectively). In the enalapril-treated group 1, 25-dihydroxyvitamin D levels (61 +/-27 and 42 +/-19 nmol/L, P =.0022) decreased. Only women presented a statistical significance (1.064 +/-0.16 g/cm(2), P =.034) between ID+II polymorphism and BMD decrease, and between DD polymorphism with less BMD under baseline conditions and a BMD increase (1.070 +/-0.16 g/cm(2), P =.017) after ACE inhibitor treatment. CONCLUSIONS: The ACE inhibitors have a beneficial effect on BMD and calcium metabolism alterations in hypertensive subjects. Concerning BMD response, women presenting with the II+ID polymorphism had a poor response to antihypertensive drug treatment, whereas women with the DD polymorphism responded better. This is the first study demonstrating a relationship between ACE polymorphism and BMD response and antihypertensive ACE inhibitor treatment.

Relationship between bone mineral density and angiotensin converting enzyme polymorphism in hypertensive postmenopausal women.

BACKGROUND: The purpose of this study was to assess the relationship between bone mineral density and insertion/deletion (I/D) angiotensin converting enzyme polymorphism (ACE) in hypertensive postmenopausal women. METHODS: Blood and urine samples from the study subjects were analyzed for calcium metabolism related parameters. Densitometry studies were conducted in the lumbar spine (L2 to L4). The ACE polymorphism was analyzed by polymerase chain reaction. RESULTS: Women with II genotype showed a higher intact parathyroid hormone (76 +/- 33 v 55 +/- 27 pg/mL and 52 +/- 26 pg/mL, P =.034) without a decrease in calciuria, and higher bone mineral density than women with ID and homozygotus deletion genotype (1.138 +/- 0.08 v 1.051 +/- 0.16 pg/mL and 1.053 +/- 0.16 pg/mL). CONCLUSIONS: The ACE polymorphism could be one of the factors causing bone mass variations.

Evaluación de la exposición al monóxido de carbono en vendedores de quioscos. Valencia, Venezuela / Evaluation of exposure to carbon monoxide among kiosk vendors in Valencia, Venezuela

Objetivos. Estudiar la intensidad de la exposición al monóxido de carbono (CO), los factores contribuyentes a esta exposici¢n y sus potenciales efectos sobre la salud en vendedores de quioscos ubicados en una avenida de alta densidad de tránsito en Valencia, Venezuela. Métodos. Se midió la concentración de CO en el aire (CO-aire) en 16 quioscos y se determinó la concentración sanguínea de carboxihemoglobina (COHb-S) en los individuos que trabajan en esos quioscos y en un grupo de control formado por docentes, estudiantes y obreros de la Universidad Simón Rodríguez, ubicada en una zona montañosa, apartada, sin contaminación ambiental aparente. Resultados. En el grupo expuesto no se encontró correlación entre las concentraciones de COHb-S y de Co-aire. La COHb-S media del grupo expuesto (2,9)fue significativamente superior a la del grupo de control (1,6) y a la concentración permisible según el método análitico empleado (1,5). Todos los síntomas de frecuencia diaria afectaron a un mayor porcentaje de individuos del grupo expuesto que del grupo de control; entre los de frecuencia diaria los mas comunes en el grupo expuesto fueron la cefalea y la fatiga. En siete quioscos (43,7) se excedieron los límites permisibles de CO-aire. Conclusiones. Aunque la COHb-S media no parece alarmante, las exposiciones al CO registradas podrían tener un impacto adverso sobre la salud de estos trabajadores, especialmente si padecieran una alteración cardiovascular o por el resultado de la acción potenciadora con otros contaminantes ambientales. Se recomienda la realización de nuevos estudios con mediciones más frecuentes y prolongadas, para ejercer medidas de prevención y control de efectos adversos para la salud y estimar la calidad del aire

Lesión ureteral yatrógena por cirugía ginecológica y obstétrica: Experiencia de 10 años en el Hospital de Especialidades del Centro Médico Nacional "La Raza" / Iatrogenic ureteral lesion by gynecologic and obstetric surgery: experience of 10 years in the Hospital de Especialidades del Centro Médico Nacional \"La Raza\"

La lesión quirúrgica del uréter es un importante problema que confrontan el urólogo y el ginecólogo. Los autores comunican su experiencia durante 10 años (junio de 1986 a junio de 1996) con los casos de 93 pacientes que experimentaron lesiones de uréter por cirugía ginecoobstétrica. Se encontraron un total de 108 lesiones de uréter: 46 por ciento de uréter izquierdo, 31.1 por ciento de uréter derecho y 16.1 por ciento bilaterales. Estas lesiones se advirtieron durante el procedimiento sólo en 13 por ciento de los casos con reparación inmediata. En la proporción restante de 86 por ciento la lñesión de diagnósticó en el periodo posoperatorio inmediato, y en un pequeño poercentaje se diagnosticó en forma tardía (3.2 por ciento). Los estudios realizados fueron urografía excretora, ultrasonido renal y pielografía escendente. Una vez establecido el diagnóstico, la reparación del uréter se realizó de inmediato, y el procedimiento de reparación que se utilizó en la mayoría de los casos fue la reimplantación ureteral

Acceso transanorrectal sagital posterior en lesiones complicadas de ureta posterior en pediatría / Posterior sagittal transanorectal access in complicated posterior urethra lesions in pediatrics

El tratamiento de las lesiones de uretra posterior (estenosis, fistula o ambas) en niños plantea diversos problemas por las limitaciones de los accesos empleados más a menudo y el tamaño pequeño y lo delicado de las estructuras. Se utilizó el acceso transanorrectal sagital posterior (ATSP) para la reparación de lesiones complejas de uretra posterior en 11 niños (nueve varones y dos mujeres). Siete de ellos habían sido sometidos a varios intentos de reparación por técnicas diversas. Se realizaron resecciones y sustancias uretral con mucosa bucal en dos casos, y sustitución uretral con colgajo recal en otro. A seis pacientes se les realizaron resección y reanastomosis primaria. Se efectuó cierre primario en dos niñas con diagnóstico de fístula uretrovaginal. El ATSP ofrece exposición y visualización excelentes de las lesiones que se van a reparar, facilitar su resección y reanastomosisprimaria, y permite la utilización de injertos libres o colgajos pediculados de estructuras vecinas. Los resultados finales fueron satisfactorios en 10 de 11 pacientes. Las complicaciones y la morbilidad relacionadas con este acceso no fueron significativas