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Background: Ankle-braquial index (ABI) is an useful tool for the diagnosis of peripheral arterial disease, but it is also an independent and positive predictor of endothelial dysfunction and cardiovascular risk. In the INDAGA study, 76% of the patients with an ABI < 0.9 were hypertensive. Inhibitors of the renin angiotensin system ameliorate vascular function and must improve the ABI. Objective: To study if the management of arterial hypertension with inhibitors of the angiotensin converting enzyme (ACEI) improves the ABI. Material and method: A study in which 30 hypertensive patients never treated with ACEI nor with antagonist of the angiotensin receptor were evaluated. Patients were treated with moexipril 7.5 mg/day, the dose was titrated to 15 mg if blood pressure values <140/90 mmHg were not reached. In all patients the ABI was registered with a 5 megahertz doppler (Summit doppler L250, Life Dop., USA) at the beginning and the end of the study 3 months later, an ABI between 0.9 and 1.3 was considered normal. Statistical analysis was performed with the Wilcoxon test. Results: In all patients a good control of blood pressure values was obtained (166/96 to 129/77 mmHg, p< 0.01), although 15 patients required increasing the dose. The ABI was modified from 0.93 to 1.03 (p<0.01), in 11 patients the management normalized the ABI above 0.9. A regression analysis showed that the improvement in the ABI was independent of the blood pressure control. Conclusion: Treating hypertension with moexipril ameliorates the ABI in hypertensive patients independently from its antihypertensive effect and explains the effect of ACEI in the improvement of cardiovascular prognosis. [ABSTRACT FROM AUTHOR]

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Objective: To compare the level of expression of the gene CTSL and its correlation with NKT cells in patients with recent-onset type 1 diabetes (T1D), their siblings, and healthy controls., Methods: Analytical cross-sectional design. Patients with T1D < 3 months evolution, their siblings, and healthy controls were included. Percentages and absolute numbers of NKT cells were measured with expression of the CTSL gene., Results: 124 subjects: with T1D (n = 48), siblings (n = 44) and controls (n = 32) were included. HbA1c was greater and C-peptide lower in T1D than the other groups and sibling age was higher (p < 0.001). There were no differences in NKT cells between T1D (0.176 ± 0.202) and controls (0.118 ± 0.133), but the percentage was higher in siblings (0.246 ± 0.188; p = 0.002). Lower level of expression of the CTSL gene associated with both absolute number (r: 0.4607; 95% CI: -0.08425 to -0.7935; p = 0.043) and percentage of NKT cells (r: 0.4540; 95% CI: -0.0927 to -0.7903; p = 0.045) in the T1D group., Conclusions: Patients with T1D have lower percentage and absolute number of NKT cells compared to their siblings. NKT cells absolute numbers are correlated with the expression of CTSL in T1D patients.

Background: Certain HLA class II haplotypes have long been related with the risk of developing type 1 diabetes. The presence of the HLA haplotype DRB1*04/DQA1*03/DQB1*03:02, together with specific β-cell autoantibodies, contributes to the development and/or severity of insulin deficiency in type 1 diabetes., Objective: To evaluate the association of HLA risk haplotype HLA-DRB1/-DQA1/-DQB1 with β-cell function and antibody markers in recent-onset type 1 diabetes patients, their siblings, and controls., Methods: We studied recently diagnosed type 1 diabetes pediatric patients, their siblings, and healthy controls, analyzing autoantibodies (anti-glutamic acid decarboxylase, anti-IA-2, and anti-insulin), HLA risk and protector haplotypes, and β-cell function (plasma proinsulin, insulin and C-peptide). X2, ANOVA or Kruskal-Wallis and multiple logistic regression were used to analyze data., Results: We included 46 patients, 72 siblings, and 160 controls. Prevalence of anti-tyrosine phosphatase-related islet antigen 2 and anti-glutamic acid decarboxylase antibodies was higher in patients than siblings and controls. We found risk haplotype DRB1*04/DQA1*03/DQB1*03:02 in 95.7% of patients vs. 51.87% of controls; DRB1*03:01/DQA1*05/DQB1*02 in 47.8% of patients vs. 8.12% of controls; and DRB1*14/DQA1*05/DQB1*03:01 in 2.2% of patients vs. 20.0% of controls. With DRB1*04/DQA1*03/DQB1*03:02, the prevalence of antibodies was significantly higher in patients, although not within any single group. In regression model based on insulin secretion, only anti-tyrosine phosphatase-related islet antigen 2 antibodies and age were associated with the risk haplotype., Conclusions: The DRB1*04/DQA1*03/DQB1*03:02 haplotype increased the risk for lower insulin, proinsulin, and C-peptide concentrations, suggesting an association with the severity of insulin deficiency in type 1 diabetes patients. This haplotype, added to antibody positivity, is a predictor of deficient insulin secretion in a Mexican pediatric population.

Omeprazole is a very widely used proton-pump inhibitor. Currently, there are several branches available in Mexico, however, limited information about their bioavailabilities is available. The purpose of this study was to compare the bioavailability of two of them, Losec and Omelcid. Twenty-eight healthy volunteers were enrolled in this study that was carried out following the recommendations of the Declaration of Helsinki. Subjects read the protocol that was approved by the institutional research and ethics committees and gave written consent for participation. After an overnight fast, volunteers received an oral dose of 20 mg omeprazole (formulation A or B) and blood samples were obtained at selected times during 8 hours. Plasma was obtained by centrifugation and stored frozen until analyzed by a validated HPLC method. Pharmacokinetic parameters were obtained by non-compartmental analysis and values (+/- s.e.m.) obtained were as follows: Cmax 354.28 +/- 51.57 and 308.95 +/- 44.42 ng/ml, t(max) 2.26 +/- 0.22 and 2.63 +/- 0.24 h and AUC(8h) 701.01 +/- 109.34 and 774.13 +/- 132.84 ngh/ml for formulations A and B respectively. Log transformed Cmax and AUC(8h) were compared by analysis of variance and 90% confidence limits of the parameters ratios (B/A) were 72.73-106.34% and 90.32-124.96%, for Cmax and AUC(8h) respectively. As confidence intervals did not exceed the 70-142.9% limits for Cmax and 80-125% for AUC(8h), it is concluded that the formulations tested are bioequivalent.

Background: Hypertension and type-2 diabetes affect endothelial function, which in turn increases the expression of soluble adhesion molecules and lead to the development of vascular damage. The aim of this study was to assess soluble adhesion molecule levels among normotensive and hypertensive diabetic patients., Material and Methods: Serum levels of soluble VCAM1, ICAM1 and e-selectin were measured in 80 type-2 diabetic patients, (40 normotensive and 40 hypertensive), and in 40 normotensive non-diabetic subjects by ELISA (RyDSystems Minneapolis). Statistical analysis was performed with ANOVA., Results: Among diabetic patients, levels of all three soluble adhesion molecules were significantly increased when compared with non-diabetic patients (p < 0.001 for all three molecules), In diabetic hypertensive patients, higher levels of ICAM1 were detected in comparison to normotensive diabetic patients (316 vs. 295 ng/ml p < 0.01), VCAM1 and e-selectin levels were not different between diabetic patients with and without hypertension., Conclusions: Diabetes is associated with increased levels of soluble adhesion molecules, suggesting a role of these molecules may play in endothelial damage. ICAM1 is further increased when hypertension and diabetes are present. The latter may explain why diabetic-hypertensive patients displayed more complications than normotensive patients.

Glyburide (glibenclamide) is a sulfonylurea derivative that is very widely used in the treatment of type II diabetes mellitus. Currently, there are several pharmaceutical formulations available in Mexico containing this drug, however, very limited information about their bioavailabilities is known. The purpose of this study was to compare the bioavailability of two formulations of glyburide used in Mexico, Daonil and Gen-Glybe. Twenty-four Mexican healthy volunteers participated in this study that was carried out following the recommendations of the Declaration of Helsinki. Subjects received a dose of 10 mg of glyburide (two tablets of 5 mg) under fasting conditions in two separate sessions using a randomized crossover design with a one week washout period. Plasma samples were obtained at selected times over 24 hours and stored frozen until analyzed. Pharmacokinetic parameters were obtained and values (mean +/- S.E.M.) were as follows: Cmax 273.32 +/- 25.84 versus 294.83 +/- 27.12 ng/ml; tmax 3.03 +/- 0.23 versus 2.87 +/- 0.24 h; and AUC24h 1396.66 +/- 130.18 versus 1557.99 +/- 140.24 ng x h/ml, for Daonil and Gen-Glybe tablets, respectively. Pharmacokinetic parameters were compared using analysis of variance for a cross-over design and ratios of AUC24h and Cmax and 90% confidence intervals were obtained. As confidence intervals did not exceed the limits of acceptance (80--125%) for Cmax and AUC24h, it is concluded that the formulations tested are bioequivalent.

In recent years, there has been an increasing prevalence of obesity and related diseases. This epidemiological change has increased the interest of researchers in the molecular and biochemical pathways involved in the pathogenesis of hepatic and biliary diseases. Insulin resistance is considered the major mechanism involved in the hepatic and biliary manifestations of obesity. Epidemiological, clinical, and basic research demonstrates that insulin resistance is associated with gallstone disease, nonalcoholic fatty liver disease, and poor outcomes in viral hepatitis C treatments. Fascinating experimental evidence demonstrates that fat-induced hepatic insulin resistance may result from the activation of kinases leading to impaired insulin signaling. The insulin-resistant state is characterized by a failure to suppress hepatic glucose production and glycogenolysis, with enhanced fat accumulation in hepatocytes because of increased lipolysis, increased free fatty acid uptake by hepatocytes, and increased hepatic synthesis of triglycerides. This molecular signaling induces a low-grade chronic inflammatory state, characterized by increased levels of proinflammatory molecules and acute-phase proteins. This review summarizes the most important molecular and biochemical issues in the hepatic and biliary diseases associated with insulin resistance.

The bioavailability of naproxen sodium (CAS 26159-34-2) after administration of two oral suspensions, reference or test (Pactens), was compared in 24 healthy subjects. The volunteers received an oral dose of 250 mg (10 ml) in two separate sessions under fasting conditions according to a randomized cross-over design and blood samples were obtained at selected times for a period of 72 h. Plasma samples were analyzed by a high-performance liquid chromatographic method for determination of naproxen. Individual plasma concentration against time curves were constructed and pharmacokinetic parameters were obtained by non-compartmental techniques. The parameters obtained (mean +/- S.E.M.) were: C(max) 43.93 +/- 1.83 and 44.91 +/- 2.15 microg/ml, t(max) 2.38 +/- 0.21 and 1.83 < or = 0.19 h, AUC(72 h) 721.73 +/- 18.47 and 722.55 +/- 19.07 microg x h/ml for reference and test formulations, respectively. Maximal concentration, AUC(72 h) and AUC(infinity). were log transformed and compared by analysis of variance and ratios; in addition, 90% confidence limits were obtained. As confidence limits were included in the 80-125% range and the probability of exceeding these intervals was always lower than 0.05, it is concluded that the formulations tested are bioequivalent.

The current study was designed to evaluate a tool for the self-identification of tapeworm carriers. Clinical and animal health care practitioners and schoolteachers were trained regarding the life cycle, risk factors, and control measures related to infection with Taenia solium. More than 120 small glass bottles with a few tapeworm segments fixed in formaldehyde and an instructional guide were distributed among all clinical practitioners (physicians and nurses) working in health centers. The guide contained 10 key points on how to ask questions about tapeworm infections. Information on taeniosis and cysticercosis was also provided to the general population via different media. Seven tapeworm carriers were recorded in the official epidemiology surveillance system the year previous to the study, compared with the year after the study, when 41 tapeworm carriers (37 Taenia saginata; 4 Taenia solium) were recorded. Six times more tapeworm carriers were notified after the study. All four persons with Taenia solium were treated, thereby eliminating the parasite and subsequently preventing any new cases of human and swine cysticercosis that might have arisen from them.

B vitamins have been used as analgesic drugs to treat pain disorders associated with their deficiency. More recently it has been claimed that B vitamins are useful to relieve different pain states as carpal tunnel, migraine and premenstrual tension. In Latin America, B vitamins are commonly used to treat neuropathic pain; however, there is no data to support this indication. In the present work we assessed the possible analgesic activity of vitamin B12 alone and combined with diclofenac in a neuropathic pain model in the rat. Neuropathic pain was induced by ligation of the left L5 and L6 spinal nerves of female Wistar rats. Tactile allodynia was determined by measuring paw withdrawal in response to probing with a series of calibrated von Frey filaments. Vitamin B12 (0.75-6 mg/kg), but not diclofenac (1-10 mg/kg), reduced in a dose-dependent manner tactile allodynia induced by spinal nerve ligation. Diclofenac (3.2 mg/kg) was not able to further increase vitamin B12-induced antiallodynia. Results indicate that vitamin B12, but not diclofenac, produces antiallodynic effects in the rat and suggest that this vitamin could be a potential treatment for neuropathic pain in humans.

The purpose of this study was to assess the possible synergistic interaction between gabapentin and B-vitamins (100:100:1 of vitamin B1, B6 and B12, respectively) in a neuropathic pain model in the rat. Neuropathic pain was induced by ligation of the left L5 and L6 spinal nerves of female Wistar rats. Tactile allodynia was determined by measuring paw withdrawal in response to probing with a series of calibrated von Frey filaments. Gabapentin (30-300 mg/kg), B-vitamins (75-600 mg/kg), or a combination of gabapentin and B-vitamins were administered orally and the antiallodynic effect was determined. Isobolographic analyses were used to define the nature of the functional interactions between gabapentin and B-vitamins in a fixed-dose ratio (0.5:0.5). Gabapentin (ED30 23.0+/-5.3 mg/kg), B-vitamins (ED30 524.0+/-97.0 mg/kg), or a fixed-dose ratio combination of gabapentin-B vitamins combinations dose-dependently reduced tactile allodynia. The theoretical ED30 value for the combination estimated from the isobologram was 273.5+/-48.6 mg/kg. This value was significantly higher than the experimental ED30 value which was 18.7+/-1.7 mg/kg. Results indicate that systemic administration of gabapentin and B vitamins can interact synergistically to reduce neuropathic pain in the rat and suggest the use of this combination to relieve neuropathy in humans.

The purpose of this study was to assess the possible synergistic interaction between ketorolac and B-vitamins in the rat formalin test. Female Wistar rats were injected into the dorsal surface of the right hind paw with 50 microl of diluted formalin (1%). Reduction of number of flinches was considered as antinociception. Ketorolac (0.32-10 mg/kg, po), B-vitamins (56-316 mg/kg), or a combination of B-vitamins (either 100:100:1 or 100:100:5 proportion of vitamin B1, B6 and B12, respectively) and ketorolac was administered orally and the antinociceptive effect was determined. Isobolographic analyses were used to define the nature of the functional interactions between B-vitamins and ketorolac in a proportion (0.5:0.5, ketorolac:B-vitamins). Ketorolac (ED25 3.5+/-0.7 mg/kg), B-vitamins in a 100:100:1 (ED25 277.1+/-30.2 mg/kg) or 100:100:5 (ED25 157.3+/-13.7 mg/kg) proportion and fixed-ratio B-vitamins-ketorolac combinations dose-dependently reduced flinching behavior during second phase of the test. Theoretical ED25 values for the combination ketorolac-B vitamins estimated from the isobolograms were 140.3+/-15.1 and 80.4+/-6.8 mg/kg for 100:100:1 and 100:100:5 proportions, respectively. These values were significantly higher than experimental ED25 values which were 73.3+/-6.3 and 47.7+/-6.4 mg/kg for 100:100:1 and 100:100:5 proportions, respectively. Results indicate that oral ketorolac and B-vitamins can interact synergistically to reduce inflammatory pain in the formalin test and suggest the use of those combinations to relief this kind of pain in humans.

The purpose of this study was to assess the possible synergistic interaction between diclofenac and B-vitamins (100:100:1 of vitamin B1, B6 and B12, respectively) in the rat formalin test. Female Wistar rats were injected into the dorsal surface of the right hind paw with 50 microl of diluted formalin (1%). Reduction of the number of flinches was considered as antinociception. Diclofenac (0.31-316 mg/kg), B-vitamins (32-178 mg/kg), or a combination of B-vitamins and diclofenac was administered orally and the antinociceptive effect was determined. Isobolographic analyses were used to define the nature of the functional interactions between B-vitamins and diclofenac in two proportions (1:1, 1:3; Diclofenac:B-Vitamins). Diclofenac (ED30 3.7+/-0.4 mg/kg), B-vitamins (ED30 76.2+/-8.5 mg/kg), and fixed-ratio B-vitamins-diclofenac combinations dose-dependently reduced flinching behavior during second phase of the test. Theoretical ED30 values for the combination estimated from the isobolograms were 39.9+/-4.2 and 58.1+/-6.4 mg/kg for 1:1 and 1:3 proportions, respectively. These values were significantly higher than experimental ED30 values which were 7.4+/-9.3 and 22.8+/-9.8 mg/kg for 1:1 and 1:3 proportions, respectively. Results indicate that oral diclofenac and B-vitamins can interact synergistically to reduce inflammatory pain in the formalin test and suggest the use of those combinations to relief this kind of pain in humans.

The combination of dexamethasone and B-vitamins is widely used in Mexico to treat neuropathic pain in human beings. However, so far there is no evidence in preclinical models about the efficacy of this combination. The purpose of this study was to assess the possible synergistic interaction between dexamethasone and the B-vitamin complex in a neuropathic pain model in the rat. Neuropathic pain was induced by ligation of the left L5 and L6 spinal nerves in female Wistar rats. Tactile allodynia was determined by measuring paw withdrawal in response to probing with a series of calibrated von Frey filaments. Dexamethasone (4-32 mg/kg), B-vitamins (75-600 mg/kg), or a combination of dexamethasone and B-vitamins (100:100:1 of vitamin B1, B6 and B12, respectively) was administered subcutaneously and the antiallodynic effect was determined. Isobolographic analyses were used to define the nature of the functional interactions between dexamethasone and B-vitamins (0.5:0.5). Dexamethasone (ED30 5.4+/-1.2 mg/kg), B-vitamins (ED30 181.1+/-2.6 mg/kg), and fixed-dose ratio dexamethasone-B-vitamins combinations dose-dependently reduced tactile allodynia in the rat. Theoretical ED30 value for the combination estimated from the isobologram was 128.2+/-5.8 mg/kg. This value was significantly higher than experimental ED30 value which was 21.8+/-2.3 mg/kg. Results indicate that subcutaneous administration of dexamethasone and B-vitamins interacted synergistically to reduce tactile allodynia in the rat and suggest the use of this combination to reduce neuropathic pain in humans.

The purpose of this study was to assess the possible synergistic interaction between gabapentin and metamizol in the rat formalin test. Female Wistar rats were injected into the dorsal surface of the right hind paw with 50 microl of diluted formalin (1%). Formalin injection induced a typical flinching behavior indicating nociception. Reduction of the number of flinches was considered as antinociception. Gabapentin (10-300 mg/kg), metamizol (30-600 mg/kg), or the combination of gabapentin and metamizol were administered orally and the antinociceptive effect in the formalin test was determined. Isobolographic analyses were used to define the nature of the functional interaction between gabapentin and metamizol in a fixed-dose ratio (0.5:0.5). Gabapentin (ED30 18.3+/-7.9 mg/kg), metamizol (ED30 139.2+/-6.2 mg/kg) and fixed-dose ratio gabapentin-metamizol combinations dose-dependently reduced flinching behavior during second phase of the test. Theoretical ED30 value for the combination estimated from the isobologram was 78.8+/-5.5 mg/kg, whereas that experimental ED30 value was 15.0+/-1.2 mg/kg. Results indicate that oral administration of gabapentin and metamizol can interact synergistically to reduce inflammatory pain in the formalin test and suggest the use of this combination to relieve pain in humans.

Urinary tract infections are one of the most common bacterial infections in female children. This infection has a prevalence of 4.1 to 7.1% during infancy. The bacterial agents causing the urinary tract infection are Escherichia coil (80-90%), followed by other gram negative germs such as Klebsiella pneumoniae and Enterococcus species and gram positive such as Staphylococcus species. Typical treatment for this infection is ampicillin or the mixture of trimethoprim and sulfamethoxazole (TMT/SMX) among others. However, a high incidence of microbial resistance to these antibiotics has been observed recently. The purpose of this study was to assess the microbial resistance of the most frequent infectious agents in urinary tract of Mexican children from January to December 2000. A total of 725 urinary cultures were collected during all year. Of these, 293 patients were positive of the most frequently reported bacteria including Escherichia coil (205 patients, 69.9%), Klebsiella pneumoniae (67 patients, 22.8%) and Proteus mirabilis (21 patients, 7.1%). Infections produced by Escherichia coil were highly resistant to ampicillin (83.5%) and TMT/SMX (76.7%). Results indicate a high incidence of microbial resistance to ampicillin and TMT/SMX in urinary tract infections in Mexican children and suggest caution before giving a treatment with antibiotic in this condition.