Anti-leishmanial compounds from microbial metabolites: a promising source.

Leishmania is a complex disease caused by the protozoan parasites and transmitted by female phlebotomine sandfly. The disease affects some of the poorest people on earth with an estimated 700,000 to 1 million new cases annually. The current treatment for leishmaniasis is toxic, long, and limited, in view of the high resistance rate presented by the parasite, necessitating new perspectives for treatment. The discovery of new compounds with different targets can be a hope to make the treatment more efficient. Microbial metabolites and their structural analogues with enormous scaffold diversity and structural complexity have historically played a key role in drug discovery. We found thirty-nine research articles published between 1999 and 2021 in the scientific database (PubMed, Science Direct) describing microbes and their metabolites with activity against leishmanial parasites which is the focus of this review. KEY POINTS: • Leishmania affects the poorest regions of the globe • Current treatments for leishmaniasis are toxic and of limited efficacy • Microbial metabolites are potential sources of antileishmania drugs.

Tissue- and breed-specific expression of the chicken fat mass- and obesity-associated gene (FTO).

The fat mass- and obesity-associated gene (FTO) is involved in energy metabolism, but little is known about the chicken FTO gene. The objective of the current study was to detect chicken FTO expression patterns in the hypothalamus, liver, and skeletal muscle during development, and analyze the effects of age and breed on FTO expression. Real-time quantitative polymerase chain reaction results revealed that chicken FTO mRNA was expressed in all of the tissues tested. Chicken FTO exhibited tissue- and breed-specific patterns in the recessive White Plymouth Rock chicken and the Qingyuan partridge chicken. The highest FTO expression level was in the hypothalami of 1-week-old chicks. FTO mRNA was expressed more in the breast muscles and livers of recessive White Plymouth Rock chickens than those of Qingyuan partridge chickens at 1 and 8 weeks of age. These results indicate that FTO probably plays a significant role in energy metabolism at 1 week old, when chicks have undergone metabolic adaptations from yolk dependence to the utilization of exogenous feed.

Hypomagnesaemia and hypocalcaemia in a patient with systemic sclerosis: role of proton pump inhibitors.

Proton pump inhibitors (PPI) are widely used in patients with systemic sclerosis (SSc) due to the chronic gastroesophageal reflux. The authors report a female patient with a 9-year history of SSc and long-term use of omeprazole, who complained of paresthesia and asthenia for 12 months. Physical examination revealed clinical signs of hypocalcaemia confirmed by laboratory tests that also showed hypomagnesaemia. After exclusion of possible causes, hypomagnesaemia secondary to PPI was diagnosed and omeprazole was replaced by a histamine H2-receptor antagonist: ranitidine. Despite continuous magnesium supplementation, the reintroduction of PPI at a lower dose due to worsening of dyspeptic symptoms led to recurrence of hypomagnesaemia. After definitive suspension of PPI, reintroduction of ranitidine and optimisation of anti-reflux environmental measures, the patient stabilised. In conclusion, SSc patients using PPIs should have their magnesium and calcium serum levels measured periodically, and non-specific symptoms such as asthenia, generalised paresthesia or life-threatening manifestations (seizures, arrhythmias) should not be neglected.

Epidemiologic surveys of histoplasmin and paracoccidioidin sensitivity in Brazil.

We report here the results obtained in epidemiologic surveys of histoplasmosis and paracoccidioidomycosis carried out in Brazil using the histoplasmin and paracoccidioidin delayed hypersensitivity skin tests. Most of these data have not been previously published in scientific journals and are now reported here in two tables respectively concerning histoplasmosis (88 surveys) and paracoccidioidomycosis (58 surveys). The guidelines to be followed in surveys of this nature are also commented upon.

Histoplasmin reaction. Comparison of a polysaccharide antigen to the filtrate antigen.

This work was planned by taking into account all the knowledge accumulated from the immunological study of paracoccidioidomycosis. It aimed at comparing a polysaccharide antigen from Histoplasma capsulatum to a classic histoplasmin with the help of intradermal tests of delayed type of hypersensitivity. Tests were applied to 115 individuals in Santo Amaro, a town in the State of São Paulo. Positive results using classic histoplasmin were obtained in 46.0% cases whereas positive results using the polysaccharide antigen at its highest concentration were obtained in 51.30% cases. The major conclusion in this investigation is that it is possible to use the polysaccharide antigen as histoplasmin instead of the filtrate antigen.

Muscarinic receptors and acetylcholinesterase activity in brain of patients with dementia.

The present paper describes the determination of muscarinic receptor number ([3H]-N-methylscopolamine binding) and acetylcholinesterase activity in six brain areas (pre-central gyrus, post-central gyrus, hippocampus, caudate nucleus, lentiform nucleus and substantia innominata) of demented patients (diagnosed by screening tests and neurological evaluation) and age-matched controls. There was a significant increase in muscarinic receptors in the hippocampus and substantia innominata (171.2 and 359.4 fmol/mg protein, respectively) of the demented group as compared with controls (123.9 and 219.0 fmol/mg protein, respectively). No changes were observed in pre- and post-central gyrus, while a tendency towards decreased binding was detected in the caudate nucleus and lentiform nucleus of the demented group. Lower acetylcholinesterase activity was also detected in the demented group in all areas studied although the differences were significant only in the post-central gyrus, caudate nucleus and substantia innominata which showed a 49, 21 and 25% decrease in enzyme activity, respectively. The results are discussed in terms of a compensatory mechanism of presynaptic deficiency such as that occurring in Parkinson's disease.