Pharmacokinetic Profile and Comparative Bioavailability of an Oral Fixed-Dose Combination of Metformin and Acetylsalicylic Acid (Aspirin).

Patients with diabetes face a 2-4-fold greater cardiovascular risk compared to those without diabetes. Both metformin and acetylsalicylic acid (aspirin) treatment have demonstrated a significant reduction in this risk. This single-center, open-label, sequence randomized, 2 × 2 crossover, single-dose clinical trial evaluated the pharmacokinetics profile and comparative bioavailability of a novel oral fixed-dose combination (FDC) of metformin/acetylsalicylic acid (500/100 mg tablet) versus the reference mono-drugs administered concomitantly, metformin 500 mg tablet and acetylsalicylic acid 100 mg tablet, in 22 healthy Mexican adult volunteers under fasting conditions. Blood samples were collected predose and at specified intervals across a 24-hour period following administration and were analyzed for metformin and salicylic acid using high-performance liquid chromatography coupled with tandem mass spectrometry. Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC0 -t), and (area under the plasma drug concentration-time cruve from 0 up to infinity (AUC0 ∞) data were within the range of 80%-125%. The results obtained from the present clinical study demonstrate the comparative bioavailability of the FDC when compared with the coadministration of reference mono-drugs. There were no adverse events or adverse reactions reported throughout the study.

A Randomized Control Trial of Dexketoprofen/Vitamin B (Thiamine, Pyridoxine and Cyanocobalamin) Fixed-Dose Combination in Post-Traumatic Grade I-II Cervical Sprains.

BACKGROUND: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders. OBJECTIVE: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains. METHODS: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0. RESULTS: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC. CONCLUSIONS: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains. CLINICAL TRIALS REGISTRATION: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).

Real-World Evidence Evaluation on the Lipid Profile, Therapeutic Goals, and Safety of the Fixed-Dose Combination of Rosuvastatin/Ezetimibe (Trezete®) in Dyslipidemia Patients.

Introduction: Cardiovascular diseases are the leading cause of death worldwide. The combination of statins and cholesterol-absorption inhibitors promotes the decrease in risk factors, such as high concentrations of LDL (low-density lipoproteins). The aim of the study was to evaluate changes in the lipid profile and the effect on therapeutic goals, as well as the safety of dyslipidemia patients treated with Rosuvastatin/Ezetimibe (Trezete®). Materials and Methods: A real-world evidence study was conducted with retrospective data collection through a review of clinical records from dyslipidemia patients treated with Trezete® in routine medical practice. Clinical records included results of biochemical markers before treatment and at least one follow up between weeks 8 and 16. Results: The study included 103 patients' clinical records (55.4% men) with a mean age of 56.0 ± 13.0 years. More than 57% of the patients had mixed dyslipidemia and a median disease progression of 3.1 (IQR, 1.5; 9.1) years. Regarding LDL concentrations, 72.8% of the patients achieved therapeutic goals according to cardiovascular risk (CVR), which was statistically significant. Similarly, 94.1% achieved goals for total cholesterol (<200 mg/dL) and 56.0% for triglycerides (<150 mg/dL), a p value <0.001. No cardiovascular events were observed. Conclusion: Trezete® shows an important clinical impact on CVR-related target markers during the treatment of dyslipidemia patients. It is relevant to mention that a significant percentage of patients achieved therapeutic goals during the first months of treatment. Fixed-dose combination therapy has shown to be as safe as monotherapy treatment. ClinicalTrials.gov Identifier: NCT04862962.

Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial.

The health crisis caused by the new coronavirus SARS-CoV-2 highlights the need to identify new treatment strategies for this viral infection. During the past year, over 400 coronavirus disease (COVID-19) treatment patents have been registered; nevertheless, the presence of new virus variants has triggered more severe disease presentations and reduced treatment effectiveness, highlighting the need for new treatment options for the COVID-19. This study evaluates the Metformin Glycinate (MG) effect on the SARS-CoV-2 in vitro and in vivo viral load. The in vitro study was conducted in a model of Vero E6 cells, while the in vivo study was an adaptive, two-armed, randomized, prospective, longitudinal, double-blind, multicentric, and phase IIb clinical trial. Our in vitro results revealed that MG effectively inhibits viral replication after 48 h of exposure to the drug, with no cytotoxic effect in doses up to 100 µM. The effect of the MG was also tested against three variants of interest (alpha, delta, and epsilon), showing increased survival rates in cells treated with MG. These results are aligned with our clinical data, which indicates that MG treatment reduces SARS-CoV2-infected patients´ viral load in just 3.3 days and supplementary oxygen requirements compared with the control group. We expect our results can guide efforts to position MG as a therapeutic option for COVID-19 patients.

Potential Therapeutic Applications of Synthetic Conotoxin s-cal14.2b, Derived from Californiconus californicus, for Treating Type 2 Diabetes.

The FDA's approval of peptide drugs such as Ziconotide or Exendin for pain relief and diabetes treatment, respectively, enhanced the interest to explore novel conotoxins from Conus species venom. In general, conotoxins can be used in pathologies where voltage-gated channels, membrane receptors, or ligands alter normal physiological functions, as in metabolic diseases such as Type 2 diabetes. In this study, the synthetic cal14.2b (s-cal14.2b) from the unusual Californiconus californicus demonstrated bioactivity on NIT-1 insulinoma cell lines stimulating insulin secretion detecting by high performance liquid chromatography (HPLC). Accordingly, s-cal14.2b increased the CaV1.2/1.3 channel-current by 35 ± 4% with a recovery τ of 10.3 ± 4 s in primary cell culture of rat pancreatic ß-cells. The in vivo results indicated a similar effect of insulin secretion on mice in the glucose tolerance curve model by reducing the glucose from 500 mg/dL to 106 mg/dL in 60 min, compared to the negative control of 325 mg/dL at the same time. The PET-SCAN with radiolabeling 99mTc-s-cal14.2b demonstrated biodistribution and accumulation in rat pancreas with complete depuration in 24 h. These findings show the potential therapeutic use of s-cal14.2b in endocrinal pathologies such as early stages of Type 2 Diabetes where the pancreas's capability to produce insulin is still effective.

The Diversified O-Superfamily in Californiconus californicus Presents a Conotoxin with Antimycobacterial Activity.

Californiconus californicus, previously named Conus californicus, has always been considered a unique species within cone snails, because of its molecular, toxicological and morphological singularities; including the wide range of its diet, since it is capable of preying indifferently on fish, snails, octopus, shrimps, and worms. We report here a new cysteine pattern conotoxin assigned to the O1-superfamily capable of inhibiting the growth of Mycobacterium tuberculosis (Mtb). The conotoxin was tested on a pathogen reference strain (H37Rv) and multidrug-resistant strains, having an inhibition effect on growth with a minimal inhibitory concentration (MIC) range of 3.52⁻0.22 µM, similar concentrations to drugs used in clinics. The peptide was purified from the venom using reverse phase high-performance liquid chromatography (RP-HPLC), a partial sequence was constructed by Edman degradation, completed by RACE and confirmed with venom gland transcriptome. The 32-mer peptide containing eight cysteine residues was named O1_cal29b, according to the current nomenclature for this type of molecule. Moreover, transcriptomic analysis of O-superfamily toxins present in the venom gland of the snail allowed us to assign several signal peptides to O2 and O3 superfamilies not described before in C. californicus, with new conotoxins frameworks.

Differential effects of metformin glycinate and hydrochloride in glucose production, AMPK phosphorylation and insulin sensitivity in hepatocytes from non-diabetic and diabetic mice.

The liver is a main target tissue of the biguanide metformin which activates AMP-activated protein kinase (AMPK). We previously reported that administration of metformin glycinate showed a greater decrease of glycated hemoglobin A1c than a placebo in patients with type 2 diabetes mellitus (T2DM). In this study, we compared the effects of metformin hydrochloride, the oral antidiabetic drug of first choice, with those of metformin glycinate in hepatocytes from non-diabetic and diabetic mice and humans. Both formulations were equally potent regard to the reduction of basal and glucagon-induced glucose production and mRNA levels of gluconeogenic enzymes (Pck1 and G6pc) in hepatocytes from C57/Bl6 mice and humans. On the contrary, phosphorylation of AMPK and its substrate acetyl CoA carboxylase (ACC) was faster in hepatocytes treated with metformin glycinate. Likewise, we found stronger reduction in hepatocytes from obese/diabetic db/db mice of glucagon-induced glucose output and more sustained AMPK phosphorylation after treatment with metformin glycinate. Importantly, insulin sensitization regarding phosphorylation of AKT (Ser473) was enhanced in hepatocytes from db/db mice or humans pretreated with metformin glycinate. In conclusion, our data indicate that metformin glycinate may be an alternative therapy against insulin resistance during obesity and/or T2DM.

Comparative Bioavailability of Metformin Hydrochloride Oral Solution Versus Metformin Hydrochloride Tablets in Fasting Mexican Healthy Volunteers.

INTRODUCTION: Metformin tablets may be challenging to swallow not only for those patients with dysphagia but also for children and the elderly. A metformin solution was developed for easier administration and flexible dose adjustment mantained with the same bioavailability of tablets. The objective of this study was to assess the single-dose oral bioavailability of metformin hydrochloride administered as an oral solution (500 mg/5 mL) compared with metformin hydrochloride 500 mg tablets in fasting Mexican healthy volunteers. METHODS: A randomized, single dose, two-period, two-sequence, crossover study design with a 7-day washout interval was conducted. Subjects were randomly assigned to receive a single dose of 500 mg metformin hydrochloride, either as an oral solution (test drug) or as a tablet (reference drug), after 10 h of fasting. Plasma samples (16) were collected over a 16-h period after drug administration. Bioequivalence was declared when the ratio for the 90% confidence intervals (CI) of the difference in the means of the log-transformed area under the concentration-time curve from time 0 to the last observed concentration time (AUC0-t), the area under the concentration-time curve extrapolated to infinite time (AUC0-∞), and the maximum plasma concentration (Cmax) of the two products were within 0.80 and 1.25 interval. Plasma concentrations were analyzed using reverse phase chromatography by tandem mass spectrometry (LC-MS/MS). Safety and tolerability of metformin were also assessed in all subjects. RESULTS: 24 subjects were enrolled and completed the study (15 female and 9 male). Test and reference metformin hydrochloride were bioequivalent during the extent of exposure since AUC0-t and Cmax 90% CIs corresponded to 89.77-101.08% and 89.63-102.48%, respectively, both being within the pre-specified acceptance range criteria (80-125%). There were two adverse events (AE) with the reference formulation that were not related to the study drug. CONCLUSIONS: Bioequivalence in healthy volunteers in fasting conditions of the two metformin hydrochloride formulations (oral solution and tablets) was established, being the difference in means of AUC0-t, AUC0-∞ and Cmax within the acceptance range (80-125%). Oral solution formulation could offer the advantages of allowing adjusted doses and easier swallowing for every patient. Plain language summary is available for this article. TRIAL REGISTRATION: National Clinical Trials Registry (RNEC by its Spanish acronym), BD METF-Sil No. 86-15. Mexican Medicine Agency (COFEPRIS) Registry: 153300410B0368. FUNDING: Laboratorios Silanes, S.A. de C.V.

In silico-designed mutations increase variable new-antigen receptor single-domain antibodies for VEGF165 neutralization.

The stability, binding, and tissue penetration of variable new-antigen receptor (VNAR) single-domain antibodies have been tested as part of an investigation into their ability to serve as novel therapeutics. V13 is a VNAR that recognizes vascular endothelial growth factor 165 (VEGF165). In the present study V13 was used as a parental molecule into which we introduced mutations designed in silico. Two of the designed VNAR mutants were expressed, and their ability to recognize VEGF165 was assessed in vitro and in vivo. One mutation (Pro98Tyr) was designed to increase VEGF165 recognition, while the other (Arg97Ala) was designed to inhibit VEGF165 binding. Compared to parental V13, the Pro98Tyr mutant showed enhanced VEGF165 recognition and neutralization, as indicated by inhibition of angiogenesis and tumor growth. This molecule thus appears to have therapeutic potential for neutralizing VEGF165 in cancer treatment.

Inflammatory Response in Preterm and Very Preterm Newborns with Sepsis.

The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation.

Effect of metformin glycinate on glycated hemoglobin A1C concentration and insulin sensitivity in drug-naive adult patients with type 2 diabetes mellitus.

AIM: This study evaluated the effect of metformin glycinate on glycated hemoglobin A1c (A1C) concentration and insulin sensitivity in drug-naive adult patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: A randomized, double-blind, placebo-controlled clinical trial was carried out in 20 patients with drug-naive T2DM. Ten subjects received metformin glycinate (1,050.6 mg) once daily during the first month and force-titrated twice daily during the second month. Ten additional patients received placebo as the control group. Before and after the intervention, metabolic profile including A1C and insulin sensitivity (euglycemic-hyperinsulinemic clamp technique) was estimated. RESULTS: A1C concentrations decreased significantly with metformin glycinate administration (8.0 ± 0.7% vs. 7.1 ± 0.9%, P = 0.008) before and after the intervention, respectively. There were significant differences in changes from baseline of A1C between groups (0.0 ± 0.7% vs. -1.0 ± 0.5% for placebo and metformin glycinate groups, respectively; P = 0.004). A reduction of ≥1% in A1C levels was reached in 60.0% of patients with metformin glycinate administration (P = 0.02). Insulin sensitivity was not modified by the intervention. CONCLUSIONS: Administration of metformin glycinate during a 2-month period showed a greater decrease in A1C concentrations than placebo in a selected group of drug-naive adult patients with T2DM.

[Evaluation of a rapid immunological test for tuberculosis diagnosis]. / Diagnóstico de tuberculosis pulmonar mediante prueba rápida inmunocromatográfica.

OBJECTIVE: To demonstrate whether patients undergoing capsulotomy Nd: YAG laser developed intraocular hypertension after the procedure. METHODS: Prospective, pre-experimental before and after 2 measurements with post-test in patients with posterior capsular opacity from the Ophthalmology Service. Measurements of intraocular pressure (IP) before capsulotomy Nd: YAG laser, and three hours and one week later. RESULTS: We studied 47 patients, 29.8 % were men and 70.2 % women. We compared between visual acuity before and one week later (Wilcoxon test p = 0.00). IP after three hours and one week later, comparisons with Friedman test were done (p =0. 002). We compared the IP prior and one week later (Wilcoxon test, with p =0.815). IP before and three hours later were obtained (p = 0.001) and IP three hours and one week later (p = 0.004). CONCLUSIONS: We found an increase in IP in the first hours after the capsulotomy Nd: YAG laser, which decrease gradually until reaching the values presented before the procedure, in not more than a week period. It is a quick and safe procedure to treat posterior capsular opacity.

[Cost-effectiveness in the detection of influenza H1N1: clinical data versus rapid tests]. / Costo-efectividad en la detección de influenza H1N1: datos clínicos versus pruebas rápidas.

OBJECTIVE: Evaluate the performance of clinical data and the rapid influenza diagnostic test (RIDT) in diagnosing influenza H1N1, and analyze the cost-benefit of using this diagnostic tool. METHODS: The RIDT was used for patients who came to four hospitals in Mexico City with an influenza-like illness (ILI) in October and November 2009. The diagnostic performance of the ILI clinical data and the RIDT was compared to that of the real-time reverse transcription polymerase chain reaction (rRT-PCR) test. The rRT-PCR test was conducted in a reference laboratory and blinded to the results of the RIDT. An economic evaluation also was conducted to estimate the budgetary impact of using the RIDT. RESULTS: The study included 78 patients, 39 of whom tested positive for influenza H1N1 and 6 tested positive for seasonal influenza A, according to the results of the rRT-PCR. The ILI clinical data yielded a sensitivity of 96% and specificity of 21%; the RIDT yielded a sensitivity of 76% and specificity of 82%; and the ILI clinical data and RIDT together yielded a sensitivity of 96% and specificity of 100%. The positive likelihood quotient for ILI-headaches was 31.5 and that of ILI-odynophagia, 330. The use of RIDT yielded savings of US$12.6 per each suspected case. CONCLUSIONS: Use of the RIDT to aid in the diagnosis of influenza H1N1 increases certainty and lowers the average cost per suspected and infected patient.

Costo-efectividad en la detección de influenza H1N1: datos clínicos versus pruebas rápidas / Cost-effectiveness in the detection of influenza H1N1: clinical data versus rapid tests

OBJETIVO: Evaluar el desempeño de los datos clínicos y la prueba rápida (PR) en el diagnóstico de influenza H1N1, y analizar el costo-beneficio que representa el uso de esta herramienta diagnóstica. MÉTODOS: Se aplicó la PR a pacientes que acudieron a cuatro hospitales en la ciudad de México con sintomatología similar a influenza (SSI) durante el período octubre y noviembre de 2009. Se comparó el desempeño diagnóstico de la SSI más la PR contra el de la reacción en cadena de la polimerasa en transcripción reversa en tiempo real (rRT-PCR). La rRT-PCR fue procesada en un laboratorio de referencia y cegado al resultado de la PR. Además, se llevó a cabo una evaluación económica a partir de la cual se estimó el impacto presupuestal relacionado con la utilización de la PR RESULTADOS: Se incluyó a 78 pacientes, de los cuales 39 fueron positivos para influenza H1N1 y 6 para influenza A estacional, de acuerdo al resultado de la rRT-PCR. La SSI mostró una sensibilidad de 96 por ciento y una especificidad de 21 por ciento, la PR de 76 por ciento y 82 por ciento y el conjunto de SSI más PR de 96 por ciento y 100 por ciento, respectivamente. El Cociente de Verosimilitud positivo de la SSI-cefalea fue de 31,5 y el de SSI-odinofagia fue de 330. El uso de PR mostró un ahorro de US$ 12,6 por cada caso sospechoso. CONCLUSIONES: El uso de la PR como auxiliar en el diagnóstico de influenza H1N1 incrementa la certeza y reduce el costo promedio por paciente sospechoso e infectado.

OBJECTIVE: Evaluate the performance of clinical data and the rapid influenza diagnostic test (RIDT) in diagnosing influenza H1N1, and analyze the cost-benefit of using this diagnostic tool. METHODS: The RIDT was used for patients who came to four hospitals in Mexico City with an influenza-like illness (ILI) in October and November 2009. The diagnostic performance of the ILI clinical data and the RIDT was compared to that of the real-time reverse transcription polymerase chain reaction (rRT-PCR) test. The rRT-PCR test was conducted in a reference laboratory and blinded to the results of the RIDT. An economic evaluation also was conducted to estimate the budgetary impact of using the RIDT. RESULTS: The study included 78 patients, 39 of whom tested positive for influenza H1N1 and 6 tested positive for seasonal influenza A, according to the results of the rRT-PCR. The ILI clinical data yielded a sensitivity of 96 percent and specificity of 21 percent; the RIDT yielded a sensitivity of 76 percent and specificity of 82 percent; and the ILI clinical data and RIDT together yielded a sensitivity of 96 percent and specificity of 100 percent. The positive likelihood quotient for ILI-headaches was 31.5 and that of ILI-odynophagia, 330. The use of RIDT yielded savings of US$12.6 per each suspected case. CONCLUSIONS: Use of the RIDT to aid in the diagnosis of influenza H1N1 increases certainty and lowers the average cost per suspected and infected patient.

Efecto del tratamiento combinado con metformina/glimepirida sobre la función endotelial en pacientes con diabetes mellitus tipo 2 evaluados mediante PET / Effects of the combined treatment with Metformin/Glimepiride on endothelial function of patients with type 2 diabetes mellitus: a positron emission tomography (PET) evaluation study

The purpose of this study was to determine the effect of treatment, with Metformin alone or with the combination of Glimepiride/Metformin, on coronary endothelial function in asymptomatic patients with recently diagnosed type 2 diabetes mellitus (DM) Methods: 16 asymptomatic patients with type DM2 and 15 healthy controls (HC) were studied. At baseline and after treatment, myocardial blood flow (MBF) was measured with 13N-ammonia Possitron Emission Tomography (PET) at rest, during cold pressor testing (CPT) and during pharmacologic stress with adenosine. The endothelial dependent vasodilation index (EDVI), myocardial flow reserve (MFR) and the percentage of the change between rest MBF and CPT MBF (%deltaMBF) were calculated as markers of endothelial function. MBF was normalized to the rate pressure product (RPP). RESULTS: EDVI and %deltaMBF were significantly lower in diabetic patients before treatment in comparison with HC demonstrating endothelial dysfunction in the former. Treatment with Glimepiride/Metformin significantly increased EDVI and %deltaMBF in diabetic patients from baseline, thus showing an improvement in coronary endothelial function.

Efficacy of glimepiride/metformin combination versus glibenclamide/metformin in patients with uncontrolled type 2 diabetes mellitus.

AIM: The aim of this study was to compare the efficacy of glimepiride/metformin combination versus glibenclamide/metformin for reaching glycemic control in patients with uncontrolled type 2 diabetes mellitus. PATIENTS AND METHODS: A randomized, double-blind, multicenter clinical trial was performed in 152 uncontrolled type 2 diabetic patients. Serum fasting and postprandial glucose, hemoglobin A1c (A1C), high-density lipoprotein cholesterol, and triglycerides were measured. After random allocation, all patients received two pills of glimepiride (1 mg)/metformin (500 mg) or glibenclamide (5 mg)/metformin (500 mg) po once a day. Dosage was increased to a maximum of four pills in order to reach the glycemic control goals (fasting glucose or=1% reduction). Statistical analyses were carried out using chi-square, ANOVA, or Student's t test. The protocol was approved by an ethics committee and met all requirements needed to perform research in human subjects; all patients gave written informed consent. RESULTS: Each study group included 76 patients. No significant differences in basal clinical and laboratory characteristics between groups were found. At the end of the study, A1C concentration was significantly lower in the glimepiride/metformin group (P=.025). A higher proportion of patients from the glimepiride group (44.6% vs. 26.8%, P<.05) reached the goal of A1C <7% at 12 months of treatment. A higher proportion of hypoglycemic events were observed in the glibenclamide group (28.9% vs. 17.1%, P<.047). CONCLUSION: Glimepiride/metformin demonstrated being more efficacious than glibenclamide/metformin at reaching the glycemic control goals with less hypoglycemic events in patients with uncontrolled type 2 diabetes mellitus.

[Effects of the combined treatment with Metformin/Glimepiride on endothelial function of patients with type 2 diabetes mellitus. A positron emission tomography (PET) evaluation study]. / Efecto del tratamiento combinado con metformina/glimepirida sobre la función endotelial en pacientes con diabetes mellitus tipo 2 evaluados mediante PET.

UNLABELLED: The purpose of this study was to determine the effect of treatment, with Metformin alone or with the combination of Glimepiride/Metformin, on coronary endothelial function in asymptomatic patients with recently diagnosed type 2 diabetes mellitus (DM) Methods: 16 asymptomatic patients with type DM2 and 15 healthy controls (HC) were studied. At baseline and after treatment, myocardial blood flow (MBF) was measured with 13N-ammonia Possitron Emission Tomography (PET) at rest, during cold pressor testing (CPT) and during pharmacologic stress with adenosine. The endothelial dependent vasodilation index (EDVI), myocardial flow reserve (MFR) and the percentage of the change between rest MBF and CPT MBF (%deltaMBF) were calculated as markers of endothelial function. MBF was normalized to the rate pressure product (RPP). RESULTS: EDVI and %deltaMBF were significantly lower in diabetic patients before treatment in comparison with HC demonstrating endothelial dysfunction in the former. Treatment with Glimepiride/Metformin significantly increased EDVI and %deltaMBF in diabetic patients from baseline, thus showing an improvement in coronary endothelial function.

Hepatitis granulomatosa por fiebre Q / Fever Q induced granulomatous hepatitis

Se informa un caso de fiebre y granulomas hepáticos característicos, cuyo diagnóstico final fue fiebre Q. El interés de tal caso radica, por un lado, en que no cuenta con antecedentes epidemiológicos y, por otro, tampoco con la presentación clínica típica

Marcadores de progresión / Markers of progression

"La carga viral en plasma es la medida de la cantidad de virus de inmunodeficiencia humana". "La prueba de carga viral se ha convertido en una medida de pronóstico y de seguimiento en el paciente infectado por VIH-1. La medición de la carga viral es predictor del tiempo en que dicho individuo desarrollará el SIDA y de su sobrevida. Determina la verdadera efectividad de los esquemas de tratamiento antirretroviral y en muchas ocasiones es el parámetro que se utiliza para valorar el inicio del tratamiento". (AU). Existen cuatro métodos para determinar la carga viral: bDNA, NASBA, RT/PCR e Hybrid. Las apartados del artículo son: Carga viral; Usos e indicaciones. Linfocitos TCD4