Pinealectomy interferes with the circadian clock genes expression in white adipose tissue

Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24‐hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev‐erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP‐citrate lyase, malic enzyme, fatty acid synthase, and glucose‐6‐phosphate dehydrogenase) was abolished in pinealectomized animals.     

Occurrence of immunoblastic B-cell lymphoma in hairy cell leukemia

A 47-year-old man, was referred for evaluation of asymptomatic splenomegaly in September 1981, and a diagnosis of hairy cell leukemia (HCL) at the initial clinical stage was made. The patient remained asymptomatic until May 1985, when splenectomy was performed because of anemia and splenomegaly. Bone marrow and liver biopsy specimens showed diffuse infiltration by abnormal tartase resistant acid phosphatase (TRAP) positive lymphocytes with typical aspect of hairy cells. Four months later, he developed fever of unknown origin and, at laparotomy, diffuse retroperitoneal lymph node enlargement and metastatic liver nodules were seen. Lymph node and liver biopsy specimens showed diffuse infiltration by abnormal large lymphocytes, which bore monoclonal surface immunoglobulin M and light chain kappa. Only six cases of non-Hodgkin's lymphoma associated with HCL have been published to date. This report describes an additional case of immunoblastic B-cell lymphoma, preceded 4 years earlier by the diagnosis of HCL.     

Grafts of porcine intestinal submucosa for repair of cervical and abdominal esophageal defects in the rat.

Porcine small intestinal submucosa (SIS) is a cell-free collagen matrix that has demonstrated its ability as scaffold material for constructive remodeling of damaged or missing tissue. The purpose of this study was to evaluate the morphology and function of esophagoplasty in rat using a porcine SIS scaffold for the repair of a semi-circumferential defect in the cervical or in the abdominal esophagus. Sixty-seven rats underwent surgical excision of the anterior wall either of the cervical or of the abdominal esophagus and subsequent repair of the defect with an SIS patch graft. Outcomes of weight gain, signs of dysphagia, hematological and serum chemistry parameters, and barium swallow studies were used to assess the progress of healing and function over a 150-day time period. The grafts were studied for gross changes and histology at predetermined time points. Ninety-four percent of the SIS-treated rats survived, showing no significant differences in survival rate between groups. The grafted animals did well, without signs of dysphagia, and gaining weight. Barium swallow studies showed no evidence of fistula, significant stenosis, or diverticula. No hematological or serum biochemistry abnormalities were found. By 150 days, the SIS graft was replaced with esophageal-derived tissues. Specimens were completely lined by keratinized stratified squamous epithelium and showed complete regeneration of muscle fibers and scarce immunoreactivity for nerve. In the rat model, a patch graft technique using porcine SIS appears to induce esophageal regrowth either in cervical and abdominal esophagus. The repair mechanism occurred through a regenerative healing process.     

Risk factors for decreased total body and regional bone mineral density in hemodialysis patients with severe secondary hyperparathyroidism.

Hyperparathyroidism contributes significantly to decreased bone mineral density (BMD) in end-stage renal disease patients, but this negative influence is not homogeneous throughout the skeleton. We studied the BMD by dual-energy X-ray absorptiometry on total body and on different regions of the skeleton in 42 patients with severe hyperparathyroidism on hemodialysis. We also evaluated the relationship between different risk factors and BMD found on the regions examined in these patients. The legs and other sites where cortical bone predominate were mostly affected, whereas trabecular bone was relatively preserved. This is probably the result of the different effects of hyperparathyroidism on cortical and trabecular bone, but we cannot rule out the interference of ectopic calcifications and sclerotic lesions of vertebral end-plates falsely increasing lumbar spine BMD. The main determinants of low total-body BMD were, in order of importance, immobility, high intact parathyroid hormone levels, low body mass index, and low albumin. Eleven patients presented with pathologic fractures, mainly in the legs, and BMD was lower in this group than in patients without fractures. In conclusion, our study makes clear that hyperparathyroidism is a great threat to bone density in hemodialysis patients, mainly in the legs, the site mostly affected by fragility fractures in our patients. Physicians must worry not only with high parathyroid hormone levels, but also with the nutritional state of these patients.     

Central effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice

Ethnopharmacological relevance

Petiveria alliacea L. (tipi) a shrub from Phytolaccaceae family is popularly used in folk medicine for treating a wide variety of disorders in South and Central America.

Aim of the study

To investigate the neuropharmacological properties on experimental animals.

Materials and methods

The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of tipi were studied to investigate its pharmacological properties in the classical behavioral models (open-field, elevated plus maze-EPM, rotarod, barbiturate-induced sleeping time, forced swimming and pentylenetetrazole (PTZ)-induced convulsions tests) using mice. These fractions were administered intraperitoneally and orally to female mice at single doses of 100 and 200 mg/kg.

Results

All these fractions decreased the locomotor activity, rearing and grooming in the open-field test, suggesting a possible central depressant action. No significant effect was evident on motor coordination of the animals in the rotarod test. On EPM, all the fractions of tipi presented a significant reduction on the time of permanence in the open arms, indicating an absence of anxiolytic-like effect. In addition, the fractions increased the immobility time in the forced swimming test and potentiated pentobarbital-induced sleeping time in mice, confirmed a probable sedative and central depressant effect. Furthermore, the fractions increased the latency to the first convulsion and the lethal time of the PTZ-induced convulsions test in the animals, confirmed its popular use as anticonvulsant.

Conclusion

Our results suggest that the fractions of P. alliacea L. contains biologically active substance(s) that might be acting in the CNS and have significant depressant and anticonvulsant potentials, supporting folk medicine use of this plant.     

Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration

The maintenance of a benign chronic Toxoplasma gondii infection is mainly dependent on the persistent presence of gamma interferon (IFN-gamma) in the central nervous system (CNS). However, IFN-gamma-activated microglia are paradoxically involved in parasitism control and in tissue damage during a broad range of CNS pathologies. In this way, nitric oxide (NO), the main toxic metabolite produced by IFN-gamma-activated microglia, may cause neuronal injury during T. gondii infection. Despite the potential NO toxicity, neurodegeneration is not a common finding during chronic T. gondii infection. In this work, we describe a significant down-modulation of NO production by IFN-gamma-activated microglia in the presence of conditioned medium of T. gondii-infected astrocytes (CMi). The inhibition of NO production was paralleled with recovery of neurite outgrowth when neurons were cocultured with IFN-gamma-activated microglia in the presence of CMi. Moreover, the modulation of NO secretion and the neuroprotective effect were shown to be dependent on prostaglandin E(2) (PGE(2)) production by T. gondii-infected astrocytes and autocrine secretion of interleukin-10 (IL-10) by microglia. These events were partially eliminated when infected astrocytes were treated with aspirin and cocultures were treated with anti-IL-10 neutralizing antibodies and RP-8-Br cyclic AMP (cAMP), a protein kinase A inhibitor. Further, the modulatory effects of CMi were mimicked by the presence of exogenous PGE(2) and by forskolin, an adenylate cyclase activator. Altogether, these data point to a T. gondii-triggered regulatory mechanism involving PGE(2) secretion by astrocytes and cAMP-dependent IL-10 secretion by microglia. This may reduce host tissue inflammation, thus avoiding neuron damage during an established Th1 protective immune response.     

Molecular pathology of well-differentiated thyroid carcinomas

The newly discovered molecular features of well-differentiated thyroid carcinomas derived from follicular cells are reviewed, within the frame of the 2004 WHO classification of thyroid tumours, under the following headings: “Follicular carcinoma”, “Papillary carcinoma”, “Follicular variant of papillary carcinoma” and “Hürthle cell tumours”. A particular emphasis is put on the meaning of PAX8–PPARγ rearrangements, RAS and BRAF mutations, and deletions and mutations of mitochondrial genes and of nuclear genes encoding for mitochondrial enzymes, for thyroid tumorigenesis.