Essential pathogenic role of endogenous IL-18 in murine diabetes induced by multiple low doses of streptozotocin. Prevention of hyperglycemia and insulitis by a recombinant IL-18-binding protein: Fc construct

IL-18 is a cytokine structurally and functionally related to IL-1 that, in synergy with IL-12, stimulates the synthesis of IFN-gamma from T lymphocytes and natural killer cells. Because IFN-gamma plays a key pathogenic role in the development of murine immunoinflammatory diabetes induced by multiple low doses of streptozotocin (STZ) we investigated the effect of negating the actions of endogenous IL-18 in this model by administering recombinant IL-18-binding protein:Fc (IL-18 bp:Fc). C57BL/6 mice were injected once daily with 40 mg/kg STZ for 5 consecutive days, day 0 being the first day of STZ challenge. Relative to control animals treated in parallel with either PBS or human IgG, mice treated from day -3 to day 7 with daily doses of 150 microg of IL-18 bp:Fc exhibited lower incidence of diabetes and milder insulitis. In contrast, mice that were treated with IL-18 bp:Fc from day 7 to day 14 exhibited clinical and histological signs of STZ-induced diabetes similar to those of control mice treated with IgG. The protective effect of IL-18 bp:Fc was accompanied by modified ex vivo immune responses, in that spleen cells and peritoneal macrophages contained fewer IFN-gamma secreting cells and released lower amounts of nitrite (an index of nitric oxide production) and IL-1beta. We conclude that intact IL-18 function is essential for the full diabetogenic effect of low dose STZ in C57BL/6 mice.     

Serum anti-Müllerian hormone dynamics during controlled ovarian hyperstimulation

BACKGROUND: The study aim was to investigate possible changes in serum anti-Müllerian hormone (AMH) levels during controlled ovarian hyperstimulation (COH), and their possible relationship with follicular development and other ovarian hormones. METHODS: A total of 93 women undergoing COH with GnRH agonist and FSH was studied prospectively. Serum levels of AMH, inhibin B, estradiol (E(2)), progesterone, testosterone and Delta(4)-androstenedione were measured when pituitary suppression was achieved (baseline), on days 6 and 8 of FSH treatment, and on the day of hCG. The number of small (<12 mm) and large (>/=12 mm) antral follicles were estimated using ultrasound. RESULTS: Serum AMH levels declined progressively (baseline, 1.21 +/- 0.11 ng/ml; day 6, 0.91 +/- 0.09 ng/ml; day 8, 0.77 +/- 0.08 ng/ml; and day of hCG, 0.53 +/- 0.06 ng/ml), whereas-as expected-the other hormone levels increased during FSH treatment. Throughout COH, serum AMH levels correlated positively with the number of small but not large antral follicles, and with inhibin B serum levels. No correlation between AMH and the other hormones was observed. CONCLUSIONS: Serum AMH levels decline gradually during multiple follicular maturation, probably reflecting the dramatic reduction in the number of small antral follicles due to COH, and confirming the scarce AMH expression by larger follicles.     

Effects of the GaAlAs diode laser (780 nm) on the periodontal tissues during orthodontic tooth movement in diabetes rats: histomorphological and immunohistochemical analysis

The purposes of the present study are to assess the effects of the GaAlAs diode laser on the periodontal tissues and to investigate its action on the alveolar bone remodeling process during orthodontic tooth movement in normoglycemic and diabetic rats. Sixty adult male Wistar rats were divided into four groups of 15 rats: normoglycemic (N), diabetic (D), laser-normoglycemic (LN), and laser-diabetic (LD) rats. Diabetes mellitus was induced by a single intravenous injection of 40 mg/kg monohydrated alloxan. The orthodontically moved tooth underwent a force magnitude of 20 cN. The laser irradiation with a continuous emission of a 780-nm wavelength, an output power of 20 mW, and a fiber probe with a spot size of 0.04 cm in diameter and an area of 0.00126 cm² were used. Moreover, an energy density of 640 J/cm² was applied in an exposition time of 40 s. Histomorphological and immunohistochemical analysis was performed. The photobiomodulation (PBM) strongly stimulated the periodontal tissue response, establishing mainly the balance between the bone formation and resorption. Intense inflammatory cell infiltration and extensive loss of bone tissue were mainly found in the D group from 14 days. The number of osteopontin-positive osteocytes was significantly greater in the LN group, followed by the LD, especially at 7 and 14 days, whereas osteoprotegerin-positive osteoblasts were significantly higher in the LN and LD groups than in the N and D groups, respectively, in all periods. The PBM strongly stimulated the alveolar bone remodeling and favored the continuous reorganization of the soft periodontal tissues, leading to the maintenance and integrity of the periodontal microstructure under orthodontic force, especially in uncontrolled diabetic rats.     

Oral Therapy,Microbiological Findings,and Comorbidity Influence the Outcome of Prosthetic Joint Infections Undergoing 2-Stage Exchange

Background

The aim of the present study was to investigate potential predictive factors of an unfavorable outcome in patients with prosthetic joint infection (PJI) undergoing 2-stage exchange.

In vivo effects of Bothrops jararaca venom on metabolic profile and on muscle protein metabolism in rats

This study investigated the in vivo effects of the Bothrops jararaca venom (BjV) on general metabolic profile and, specifically, on muscle protein metabolism in rats. The crude venom (0.4 mg/kg body weight, IV) was infused in awake rats, and plasma activity of enzymes and metabolites levels were determined after 1, 2, 3, and 4 hours. BjV increased urea, lactate, and activities of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase after 4 hours. The content of liver glycogen was reduced by BjV. Protein metabolism was evaluated by means of microdialysis technique and in isolated muscles. BjV induced increase in the muscle interstitial-arterial tyrosine concentration difference, indicating a high protein catabolism. The myotoxicity induced by this venom is associated with reduction of protein synthesis and increase in rates of overall proteolysis, which was accompanied by activation of lysosomal and ubiquitin-proteasome systems without changes in protein levels of cathepsins and ubiquitin-protein conjugates.     

Central inferior bisegmentectomy (S4B+S5) for gallbladder carcinoma treatment: a series of seven resectable cases

BACKGROUND: Despite its rarity, gallbladder cancer is an aggressive type of neoplasia with a very poor prognosis. The best resection for oncological purposes continues to be right hepatectomy extended to segment IV. However, bisegmentectomy IV-V is becoming an interesting alternative because of greater preservation of the parenchyma. AIM: To report the early and late results from bisegmentectomy IV-V in cases of carcinoma of the gallbladder. METHODS: A series of seven cases of invasive carcinoma is presented (six women and one man). These patients underwent bisegmentectomy IV-V at the General Surgery Service of the Teaching Hospital of the ABC Medical School, Santo André, SP, Brazil. The study was conducted between 2002 and 2006. The patients ages ranged from 52 to 72 years. The diagnosis was preoperative (radiological) in five cases, which were all confirmed by intraoperative frozen-tissue examination, while in two cases the diagnosis was postoperative, following open cholecystectomy. RESULTS: The duration of the operation ranged from 180 to 340 minutes. The quantity of intraoperative bleeding ranged from 200 to 1500 mL. There were two major complications but no mortality. Six patients did not present any recurrence over the course of 3 to 30 months of follow-up. CONCLUSION: Bisegmentectomy IV-V may constitute a curative surgical alternative for treating gallbladder cancer. This procedure presents acceptable morbidity and mortality.