Muscle-specific deletion of SOCS3 does not reduce the anabolic response to leucine in a mouse model of acute inflammation.

Excessive inflammation reduces skeletal muscle protein synthesis leading to wasting and weakness. The janus kinase/signal transducers and activators of transcription-3 (JAK/STAT3) pathway is important for the regulation of inflammatory signaling. As such, suppressor of cytokine signaling-3 (SOCS3), the negative regulator of JAK/STAT signaling, is thought to be important in the control of muscle homeostasis. We hypothesized that muscle-specific deletion of SOCS3 would impair the anabolic response to leucine during an inflammatory insult. Twelve week old (n=8 per group) SOCS3 muscle-specific knockout mice (SOCS3-MKO) and littermate controls (WT) were injected with lipopolysaccharide (LPS, 1mg/kg) or saline and were studied during fasted conditions or after receiving 0.5g/kg leucine 3h after the injection of LPS. Markers of inflammation, anabolic signaling, and protein synthesis were measured 4h after LPS injection. LPS injection robustly increased mRNA expression of inflammatory molecules (Socs3, Socs1, Il-6, Ccl2, Tnfα and Cd68). In muscles from SOCS3-MKO mice, the Socs3 mRNA response to LPS was significantly blunted (∼6-fold) while STAT3 Tyr705 phosphorylation was exacerbated (18-fold). Leucine administration increased protein synthesis in both WT (∼1.6-fold) and SOCS3-MKO mice (∼1.5-fold) compared to basal levels. LPS administration blunted this effect, but there were no differences between WT and SOCS3-MKO mice. Muscle-specific SOCS3 deletion did not alter the response of AKT, mTOR, S6 or 4EBP1 under any treatment conditions. Therefore, SOCS3 does not appear to mediate the early inflammatory or leucine-induced changes in protein synthesis in skeletal muscle.

Spatial interactions in amblyopia: effects of stimulus parameters and amblyopia type.

Adults with amblyopia were recently shown to perform abnormally in tasks requiring integration of local features into global percepts. Moreover, spatial interactions in amblyopic patients, though often found to be abnormal, showed marked variability. Here we measured collinear lateral interactions using Gabor patches in a large number of amblyopic (N=75) and normal subjects (N=25), testing four spatial frequencies (1.5, 3, 6, 9 cpd). We used the lateral masking paradigm, in which the contrast-detection threshold is measured in the presence of high-contrast flankers at different distances from a central target. Whereas in normal subjects spatial interaction patterns were evident across all spatial frequencies, amblyopic subjects showed abnormal spatial interactions and increasing deficiencies with increasing spatial frequencies. These abnormalities depended on the axis of astigmatism (in meridional amblyopia) and were more pronounced in strabismic than in anisometropic amblyopia. Spatial interactions were independent on the contrast-detection thresholds. Thus, adults with amblyopia might perform as well as normal observers for some stimulus parameters and abnormally for others. Our results indicate a close relationship between abnormal visual input to the visual cortex during development and abnormal functionality of the collinear spatial interactions in adults with amblyopia.

Preoperative simultaneous fractionated cisplatin and radiation therapy in the treatment of advanced operable stage III and IV squamous cell carcinoma of the head and neck.

BACKGROUND: In Stage III/IV head and neck squamous cell carcinoma of the head and neck, multidisciplinary treatment is not standardized. This study evaluated preoperative simultaneous radiation therapy and Cisplatin 20 mg/M(2)/4 days during weeks 1, 4, and 7 of irradiation (CTRT). METHODS: Records of 143 CTRT and 48 patients treated with other surgery/radiation/chemotherapy regimens (CONTROL) were reviewed. Chi-square, analysis of variance, and Kaplan-Meier statistical analysis were performed. RESULTS: CTRT improved outcomes in Grade 2 to 5 toxicity (76% CONTROL vs 45% CTRT, P < .0001), complete clinical response (68% CTRT vs 36% CONTROL, P < .003), histologic complete response (67% in CTRT vs 28% in CONTROL, P = .0002), recurrence (33% in CTRT vs 66% in CONTROL, P = .0007), and distant metastases (2% CTRT vs 37% CONTROL, P = .0003); Kaplan-Meier disease-free survival was 65% CTRT versus 34% CONTROL. CONCLUSIONS: CTRT increases complete clinical response, histologic complete response, organ preservation, and survival, with lower recurrence and reduced toxicity and rare recurrence. CTRT may be the first treatment for Stage III/IV head and neck squamous cell carcinoma of the head and neck.

Early postoperative intraocular pressure pattern in glaucomatous and nonglaucomatous patients.

PURPOSE: To evaluate intraocular pressure (IOP) changes in the 24 hours following cataract extraction in glaucomatous and nonglaucomatous patients. SETTING: General Eye Service and Glaucoma Service of the Goldschleger Eye Institute, Tel Hashomer, Israel. METHODS: Twenty-six nonglaucomatous patients and 13 glaucomatous patients scheduled for routine cataract extraction and intraocular lens implantation were evaluated. In each patient, IOP was measured before cataract surgery and every 4 hours for 24 hours postoperatively. Thirteen of the nonglaucomatous patients were randomly treated with one drop of timolol maleate at the end of surgery (NG-T group). The other 13 nonglaucomatous patients (NG group) and all glaucoma patients (G group) were not treated. RESULTS: In the NG group, mean preoperative IOP was 13.9 mm Hg. Following surgery, IOP rose steadily to 22.2 mm Hg at 12 hours; it returned to almost presurgical levels at 24 hours. The IOP exceeded 35 mm Hg in only one patient. In the NG-T group, mean preoperative IOP was 16.5 mm Hg and increased to 21.2 mm Hg at 12 hours. The IOP returned to almost presurgical levels at 24 hours. In the G group, mean IOP was 18.8 mm Hg preoperatively and rose to 29.9 mm Hg at 8 hours after surgery. In seven eyes the IOP exceeded 35 mm Hg. COMMENTS: Our findings of elevated IOP emphasize the need for prophylactic treatment (medical or combined cataract and glaucoma surgery) to prevent IOP spikes in high-risk patients.

A study on the analysis of ochratoxin-A in different poultry feed ingredients.

A study to assess ochratoxin content in different feed ingredients was conducted. Out of 156 samples of feed ingredients analyzed 36 were found contaminated with ochratoxin. The highest content was detected in maize (*84.4 microg/kg) while millet contained the minimum content (5 microg/kg). 120 samples i.e. 77% were found to be free of ochratoxin and 23% were contaminated. In the light of these results it is suggested that proper harvesting, storage of feed be done and unhygienic method of processing and production be avoided.

In vitro effects of acth on pigeon crop-sac epithelium.

ACTH in vitro produces non-specific crop-sac epithelium response. Crop-sac maintained in 10 IU.ACTH in isologous serum at 37 degrees C for 6 hrs. showed an increase of 105 +/- 0.95 mg for 12 hrs. 115 +/- 1.13 mg, for 18 hr. 125 +/- 0.95 mg. and for 24 hrs. 145 +/- 2.31 mg. The results were analyzed statistically by ANOVA technique. A significant rise in mean weight. In ACTH treated crop-sac, indicates a time related relationship (P < 0.01, ANOVA, Table 2). Thus present data indicates that there is a correlation between the epithelial response and initiation of ACTH present in the serum.