Effects of growth hormone on glucose and fat metabolism in human subjects.

This article focuses on in vivo data from tests performed in normal subjects and in patients who had abnormal growth hormone (GH) status. Experimental data in human subjects demonstrate that GH acutely inhibits glucose disposal in skeletal muscle. At the same time GH stimulates the turnover and oxidation of free fatty acid (FFA), and experimental evidence suggests a causal link between elevated FFA levels and insulin resistance in skeletal muscle. Observational data in GH-deficient adults do not indicate that GH replacement is associated with significant impairment of glucose tolerance, but it is recommended that overdosing be avoided and glycemic control be monitored.     

Compressed collagen sponges as gastroretentive dosage forms: in vitro and in vivo studies.

The objective of the present investigations was to develop oblong tablets which expand after contact with gastrointestinal fluids within a few minutes to a length of 4-6 cm and which should remain in the stomach for a prolonged period of time due to their size. The tablets were prepared from riboflavin-containing collagen sponges using a computer controlled single punch tablet machine. The collagen material was compressed to oblong tablets with dimensions of 3.5 mm x 9 mm x 18 mm. In vitro investigations were carried out to characterise drug release. The model drug riboflavin was released from the collagen tablets over 12h. The gastrointestinal retention time of the new dosage form was indirectly estimated by determining the duration of riboflavin excretion after oral intake of the tablet. A crossover in vivo study with 12 healthy male and female subjects was performed. The renal excretion of riboflavin was measured after oral administration of collagen tablets and small sustained release hydrocolloid tablets as reference preparation. The amount of riboflavin excreted into the urine was enhanced after administration of the expanding collagen tablets in comparison with the hydrocolloid tablets. The differences were statistically significant after 5, 6, 8, 9, 10 and 12 h.     

Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer.

Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables.Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC.     

Prenatal nicotine exposure increased duration of nicotine-induced analgesia in adult rats

The effect of prenatal exposure to nicotine on nicotine-induced analgesia was studied in rats. The analgesic effect of a single dose of nicotine (1 mg/kg SC) was measured by the tail-flick technique, and two subsequent studies were carried out. In the first study, 7-month-old male rats, born to dams chronically treated with nicotine during pregnancy (NIC), exhibited prolonged nicotine-induced analgesia compared to matched controls. The second study was designed to explore whether rats prenatally exposed to nicotine (NIC rats) are born with an increased sensitivity to nicotine and whether there is any sex difference. The analgesic effect of nicotine was tested on control and NIC rats of both sexes once a month from 2 to 7 months of age. At an early age, male but not female NIC rats, exhibited shorter analgesic responses to nicotine than did the matched controls. With increasing age, however, the duration of nicotine analgesia began to be prolonged in NIC rats of both sexes. Significant differences between control and NIC rats were found at the age of 6 and 7 months, in both sexes. Thus, rats prenatally exposed to nicotine are not born with an increased sensitivity to the analgesic effect of a single dose of nicotine. This phenomenon develops later, during the course of life, independently of gender.     

Interpreting cerebrospinal fluid pleocytosis in HIV in the era of potent antiretroviral therapy

Background  

Cerebrospinal fluid (CSF) pleocytosis may be seen in asymptomatic HIV-infected individuals. This finding complicates interpretation of CSF abnormalities when such individuals are evaluated for other central nervous system infections. The goal of this study was to determine the relationship between CSF pleocytosis, central nervous system (CNS) antiretroviral penetration, adherence to antiretroviral medication regimens, neurological symptoms and performance on neuropsychological tests.     

Relationship Among MRTA, DXA, and QUS

Dual-energy X-ray absorptiometry (DXA) and quantitative ultrasound (QUS) are the accepted modalities for the evaluation of fracture risk in the clinical setting. However, neither method provides a direct measurement of bone mechanics. In this study, we investigated a prototype device, known as a mechanical response tissue analyzer (MRTA), which provides direct mechanical measurements of mechanical properties of bone. A total of 56 healthy volunteers (20 men and 36 women) between the ages of 18 and 83 were recruited. The MRTA was used to measure the cross-sectional bending stiffness (EI) of the ulna bone. Axial speed of sound (SOS) at the ulna bone was determined by QUS; bone mineral content (BMC) and bone mineral density (BMD) were determined by DXA. Correlations, regression analysis, and analyses of variance (ANOVAs) were used to compare the three modalities. These analyses revealed that although there are strong linear relationships among the data collected by the various technologies, the bone properties reflected by MRTA are not fully explained by DXA and QUS. We conclude that the total information conveyed by MRTA measurements is unique. Further research is needed to delineate the different qualities of bone strength that are captured by MRTA, but not by DXA or QUS.