Effectiveness and safety of glimepiride and iDPP4, associated with metformin in second line pharmacotherapy of type 2 diabetes mellitus: systematic review and meta-analysis.

OBJECTIVE: Our review analyses the studies that have specifically compared the association iDPP4/metformin with glimepiride/metformin, both in second line pharmacotherapy of type 2 diabetes mellitus (DM2). METHODS: Systematic literature review with a meta-analysis of clinical trials comparing glimepiride with any iDPP4, both used together with metformin as a second line treatment of DM2. The effectiveness variables used were as follows: %HbA1c variation, fasting plasma glucose variation, patients achieving the therapeutic objective of HbA1c <7%, treatment dropouts due to lack of effectiveness and rescue treatments needed. The safety variables included were as follows: weight variation at the end of treatment; presentation of any type of adverse event; presentation of serious adverse events; patients who experienced any type of hypoglycaemia; patients who experienced severe hypoglycaemia; treatments suspended due to adverse effects; and deaths for any reason. RESULTS: Four studies met the inclusion criteria. The group treated with glimepiride showed better results in all effectiveness variables. Regarding safety variables, the main differences observed were in the greater number of cases with hypoglycaemia in the group treated with glimepiride, and the serious adverse events or treatment discontinuations due to these which occurred in slightly over 2% more cases in this group compared to the iDPP4 group. The remaining adverse events, including mortality, did not show any differences between both groups. The variation in the weight difference between groups (2.1 kg) is not considered clinically relevant. CONCLUSIONS: A greater effectiveness is seen in the glimepiride/metformin association, which should not be diminished by slight differences in adverse effects, with absence of severe hypoglycaemia in over 98% of patients under treatment. The association of glimepiride/metformin, both due to cost as well as effectiveness and safety, may be the preferential treatment for most DM2 patients, and it offers a potential advantage in refractory hyperglycemic populations, tolerant to treatment.

Cloning, sequencing and expression in the dog of the main amyloid precursor protein isoforms and some of the enzymes related with their processing.

Alzheimer's disease (AD) is characterized by neuronal loss and the presence of both neurofibrillary tangles and senile plaques in the brain. These plaques arise from the deposition of beta-amyloid (Aß) peptides (38-43 amino acids), which are generated from enzymatic cleavage of the amyloid precursor protein (APP) by ß- and γ-secretases. In the present work, we cloned the principal APP isoforms as well as some enzymes that have been implicated in their amyloidogenic and non-amyloidogenic processing in dogs. Additionally, the main proteases implicated in the degradation of Aß were also studied. We also investigated the level of expression of these APP isoforms and enzymes in different brain regions and in peripheral tissues. Our data demonstrate that these canine proteins are highly homologous to their human counterparts. In addition, the expression pattern of these proteins in dogs is consistent with previous data reported in human beings. Thus, dogs may be a natural model to study the biology of AD and could also serve as an animal model for Aß-targeted drugs against this devastating disease.

Hipertensión en paciente depresivo / Hypertension in depressive patient

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Chitotriosidase genotype and serum activity in subjects with combined hyperlipidemia: effect of the lipid-lowering agents, atorvastatin and bezafibrate.

Chitotriosidase, an enzyme involved in the degradation of chitin-containing pathogens with unclear function in humans, has been proposed as a marker of lipid accumulation in macrophages in different lipid-storage diseases, including atherosclerosis. To evaluate (1) if lipid-lowering treatment could modify serum chitotriosidase activity and (2) be useful in monitoring lipid-lowering treatment, we have analyzed this enzyme activity in the participants in the Atozvastatin Versus Bezafibrate in Mixed Hyperlipidemia (ATOMIX) study, a double-blind, comparative, and randomized study comparing the efficacy of atorvastatin and bezafibrate in mixed hyperlipidemia. Because a common genetic deficiency of chitotriosidase modifies serum quitotriosidase activity, this genetic variation was also studied. Seven subjects of 116 (6.03%) were homozygous, and 46 (39.6%) were heterozygous for the defective allele. Mean serum quitotriosidase activity correlated with allele dosage, as it was found to be of 0, 59.8 +/- 52.6 and 81.2 +/- 41.6 nmol/mL/h, in homozygotes for the defective allele, heterozygotes, and homozygotes for the wild-type allele, respectively (P =.0011 for the difference between the last 2 groups). However, this enzyme activity was not found to correlate with lipid levels before and after treatment with either atorvastatin or bezafibrate, and neither with the intensity of the lipid lowering. These results do not support the use of serum chitotriosidase activity as a biologic marker of atherosclerotic plaque modification related to hypolipidemic treatment.

[Granulomatous hepatitis caused by Q fever]. / Hepatitis granulomatosa por fiebre Q.

We inform of one case of fever and characteristic hepatic granuloma in which the final diagnosis was Q fever. The interest of this case lies in the fact that the patient did not have the usual epidemiological antecedent and its typical clinical presentation.