Pharmacokinetics of amoxicillin in obese and nonobese subjects.

AIMS: To compare the pharmacokinetics of amoxicillin (AMX) in obese and nonobese subjects, given as single dose 875-mg tablets. METHODS: A prospective, single-centre, open-label, clinical study was carried out involving 10 nonobese and 20 obese subjects given a dose of an AMX 875-mg tablet. Serial blood samples were collected between 0 and 8 hours after administration of AMX and plasma levels were quantified by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters (PK) were calculated by noncompartmental analysis and means of the 2 groups were compared using Student t-test. Analysis of correlation between covariates and PK was performed using Pearson's correlation coefficient. RESULTS: Ten nonobese subjects (mean age 30.6 ± 7.12 y; body mass index 21.56 ± 1.95 kg/m2 ) and 20 obese subjects (mean age 34.47 ± 7.03 y; body mass index 33.17 ± 2.38 kg/m2 ) participated in the study. Both maximum concentration (Cmax ; 12.12 ± 4.06 vs. 9.66 ± 2.93 mg/L) and area under the curve (AUC)0-inf (34.18 ± 12.94 mg.h/L vs. 26.88 ± 9.24 mg.h/L) were slightly higher in nonobese than in obese subjects, respectively, but differences were not significant. The volume of distribution (V/F) parameter was statistically significantly higher in obese compared to nonobese patients (44.20 ± 17.85 L vs. 27.57 ± 12.96 L). Statistically significant correlations were observed for several weight metrics vs. AUC, Cmax , V/F and clearance, and for creatinine clearance vs. AUC, Cmax and clearance. CONCLUSION: In obese subjects, the main altered PK was V/F as a consequence of greater body weight. This may result in antibiotic treatment failure if standard therapeutic regimens are administered.

Vitamin E and organic selenium for broilers from 22 to 42 days old: performance and carcass traits

ABSTRACT This study was conducted to evaluate the effect of vitamin E and selenium on performance, viability, productive efficiency, and yields of carcass, major cuts, and organs of broilers from 22 to 42 days submitted to cyclic-heat stress. The experimental design was randomized blocks, in a 2 × 3 factorial arrangement with two levels of selenium (0.1 and 0.3 mg/kg) and three levels of vitamin E (300, 400, and 500 mg/kg), plus a control treatment. Animals were submitted to a natural condition of high cyclic temperature. Organic selenium levels of 0.1 and 0.3 mg/kg associated with 300, 400, and 500 mg/kg of vitamin E were tested. The level of vitamin E did not affect the performance or production efficiency of broilers in the period from 22 to 33 days and 22 to 42 days. However, the selenium inclusion level of 0.3 mg/kg improved the viability in both phases. The yields of carcass, major cuts, intestine, and heart were not influenced by the levels of selenium and vitamin E, whereas abdominal fat for the selenium level 0.1 mg/kg decreased linearly with the inclusion in vitamin E.

Vitamin E and organic selenium for broilers from 22 to 42 days old: performance and carcass traits.

This study was conducted to evaluate the effect of vitamin E and selenium on performance, viability, productive efficiency, and yields of carcass, major cuts, and organs of broilers from 22 to 42 days submitted to cyclic-heat stress. The experimental design was randomized blocks, in a 2 × 3 factorial arrangement with two levels of selenium (0.1 and 0.3 mg/kg) and three levels of vitamin E (300, 400, and 500 mg/kg), plus a control treatment. Animals were submitted to a natural condition of high cyclic temperature. Organic selenium levels of 0.1 and 0.3 mg/kg associated with 300, 400, and 500 mg/kg of vitamin E were tested. The level of vitamin E did not affect the performance or production efficiency of broilers in the period from 22 to 33 days and 22 to 42 days. However, the selenium inclusion level of 0.3 mg/kg improved the viability in both phases. The yields of carcass, major cuts, intestine, and heart were not influenced by the levels of selenium and vitamin E, whereas abdominal fat for the selenium level 0.1 mg/kg decreased linearly with the inclusion in vitamin E.

Downregulation of PHEX in multibacillary leprosy patients: observational cross-sectional study.

BACKGROUND: Peripheral nerve injury and bone lesions, well known leprosy complications, lead to deformities and incapacities. The phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) encodes a homonymous protein (PHEX) implicated in bone metabolism. PHEX/PHEX alterations may result in bone and cartilage lesions. PHEX expression is downregulated by intracellular Mycobacterium leprae (M. leprae) in cultures of human Schwann cells and osteoblasts. M. leprae in vivo effect on PHEX/PHEX is not known. METHODS: Cross-sectional observational study of 36 leprosy patients (22 lepromatous and 14 borderline-tuberculoid) and 20 healthy volunteers (HV). The following tests were performed: PHEX flow cytometric analysis on blood mononuclear cells, cytokine production in culture supernatant, 25-hydroxyvitamin D (OHvitD) serum levels and (99m)Tc-MDP three-phase bone scintigraphy, radiography of upper and lower extremities and blood and urine biochemistry. RESULTS: Significantly lower PHEX expression levels were observed in lepromatous patients than in the other groups (χ(2) = 16.554, p < 0.001 for lymphocytes and χ(2) = 13.933, p = 0.001 for monocytes). Low levels of 25-(OHvitD) were observed in HV (median = 23.0 ng/mL) and BT patients (median = 27.5 ng/mL) and normal serum levels were found in LL patients (median = 38.6 ng/mL). Inflammatory cytokines, such as TNF, a PHEX transcription repressor, were lower after stimulation with M. leprae in peripheral blood mononuclear cells from lepromatous in comparison to BT patients and HV (χ(2) = 10.820, p < 0.001). CONCLUSION: Downregulation of PHEX may constitute an important early component of bone loss and joint damage in leprosy. The present results suggest a direct effect produced by M. leprae on the osteoarticular system that may use this mechanism.

Primary monophasic synovial sarcoma of the kidney: a case report and review of literature.

Primary synovial sarcoma (SS) of the kidney is a rare neoplasm and its presenting features are similar to other common renal tumors, making early diagnosis difficult. To date, few cases have been reported in the literature. Primary renal SSs can exist in either a monophasic or a biphasic pattern, the former being more common and tending to have a better prognosis than the biphasic variant. Herein we describe a case of primary renal SS that was diagnosed based on histopathology and immunohistochemistry after radical nephrectomy. Fusion gene product analysis was also done by FISH and RT-PCR. Patient follow-up and literature review are presented, focused on systemic therapy. We highlight that these tumors should be correctly diagnosed as clinical results and specific treatment are distinct from primary epithelial renal cell carcinoma. Adjuvant chemotherapy should be tailored for each patient in the management of disease, although its role still remains unclear.

Expression of integrin genes and proteins in progression and dissemination of colorectal adenocarcinoma.

BACKGROUND: This study aimed to evaluate the relationship between the expression levels of selected integrin genes and proteins and cell differentiation, TNM stage, histological type and other variables potentially associated with the progression and dissemination of colorectal carcinoma (CRC). METHODS: A total of 114 patients (63 men and 51 women) were treated for CRC between 2006 and 2009, including 25 (21.9%) TNM I, 39 (34.2%) TNM II, 34 (29.8%) TNM III, and 16 (14.1%) TNM IV. Regarding grade, 91 (79.8%) were grade II, 14 (12.2%) were grade III and nine (7.8%) were grade I. Reverse-transcription polymerase chain reaction (RT-PCR) and tissue microarray (TMA) methods were used to examine the expression levels of the genes ITGAV, ITGA3, ITGA5, ITGB5, and ITGA6, and their proteins, respectively. RESULTS: In relation to TNM staging, ITGB5 and ITGA3 were over-expressed in stages III versus I. These results were confirmed by TMA analysis. In terms of age, ITGA5 was under-expressed according to RT-PCR, but over-expressed by TMA in patients over 60 years, while ITGA5 gene and protein levels were increased in mucinous carcinomas. In addition ITGAV gene and protein levels were elevated in tumors with neural invasion, and ITGA6 gene and protein were over-expressed in cases with venous invasion. All these results were significant at P < 0.05. CONCLUSION: The results of this study suggest that over-expression of some integrins is associated with TNM III stage, increased risk of vascular and neural invasion, and mucinous histology in patients with CRC.

Mycobacterium leprae downregulates the expression of PHEX in Schwann cells and osteoblasts.

Neuropathy and bone deformities, lifelong sequelae of leprosy that persist after treatment, result in significant impairment to patients and compromise their social rehabilitation. Phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) is a Zn-metalloendopeptidase, which is abundantly expressed in osteoblasts and many other cell types, such as Schwann cells, and has been implicated in phosphate metabolism and X-linked rickets. Here, we demonstrate that Mycobacterium leprae stimulation downregulates PHEX transcription and protein expression in a human schwannoma cell line (ST88-14) and human osteoblast lineage. Modulation of PHEX expression was observed to a lesser extent in cells stimulated with other species of mycobacteria, but was not observed in cultures treated with latex beads or with the facultative intracellular bacterium Salmonella typhimurium. Direct downregulation of PHEX by M. leprae could be involved in the bone resorption observed in leprosy patients. This is the first report to describe PHEX modulation by an infectious agent.

Mycobacterium leprae downregulates the expression of PHEX in Schwann cells and osteoblasts

Neuropathy and bone deformities, lifelong sequelae of leprosy that persist after treatment, result in significant impairment to patients and compromise their social rehabilitation. Phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) is a Zn-metalloendopeptidase, which is abundantly expressed in osteoblasts and many other cell types, such as Schwann cells, and has been implicated in phosphate metabolism and X-linked rickets. Here, we demonstrate that Mycobacterium leprae stimulation downregulates PHEX transcription and protein expression in a human schwannoma cell line (ST88-14) and human osteoblast lineage. Modulation of PHEX expression was observed to a lesser extent in cells stimulated with other species of mycobacteria, but was not observed in cultures treated with latex beads or with the facultative intracellular bacterium Salmonella typhimurium. Direct downregulation of PHEX by M. leprae could be involved in the bone resorption observed in leprosy patients. This is the first report to describe PHEX modulation by an infectious agent.