Chroman and tetrahydroquinoline ureas as potent TRPV1 antagonists

Novel chroman and tetrahydroquinoline ureas were synthesized and evaluated for their activity as TRPV1 antagonists. It was found that aryl substituents on the 7- or 8-position of both bicyclic scaffolds imparted the best in vitro potency at TRPV1. The most potent chroman ureas were assessed in chronic and acute pain models, and compounds with the ability to cross the blood-brain barrier were shown to be highly efficacious. The tetrahydroquinoline ureas were found to be potent CYP3A4 inhibitors, but replacement of bulky substituents at the nitrogen atom of the tetrahydroisoquinoline moiety with small groups such as methyl can minimize the inhibition.     

Ways of coping as predictors of satisfaction with curriculum and academic success in medical school

The purpose of the present study was to determine the coping strategies of medical students and to investigate the effects of coping strategies on student satisfaction and academic achievement with different instruction methods. A total of 152 medical students was followed throughout the first 2 yr of medical education between 2008 and 2010. Students completed a sociodemographic questionnaire and revised form of the Ways of Coping questionnaire both at the beginning of the first year and at the end of the second year. These forms provided data about the characteristics and main coping strategies (problem focused or emotion focused) of the students and revealed the change over time. At the end of the second year, participants also completed a satisfaction questionnaire asking their satisfaction with lectures, problem-based learning, and practicals. The authors used block, problem-based learning, and practical exam scores of the students attained in the past 2 yr as academic achievement indicators. No sociodemographic variable was related to coping strategy. The majority of students (80.9%) adopted problem-focused coping. A shift occurred in the main coping strategies of some students in both sides. Problem-focused coping scores decreased over time. Problem-focused coping positively correlated with satisfaction with practicals and practical exam scores, whereas emotion-focused coping showed the same correlation negatively. The main coping strategy also predicted satisfaction and exam success in practicals. In conclusion, a main coping strategy may be helpful to predict student satisfaction and academic achievement with some student-centered instruction methods. Determining undesired coping strategies may provide an opportunity for intervention to prevent relevant dissatisfaction and failure.     

Investigating paraoxonase-1 gene Q192R and L55M polymorphism in patients with renal cell cancer

Increased oxidative stress can help promote carcinogenesis, including development of renal cell carcinoma. The enzyme protects low-density lipoproteins from oxidation and can be a factor in this process. PON1 Q192R and L55M paraoxonase gene polymorphisms were assessed in 60 renal cell carcinoma patients and 60 healthy controls. Genotypes were examined by PCR; the restriction enzyme AlwI was used to examine the Q192R polymorphism and Hsp92II for the L55M polymorphism. Significant differences in the PON1 Q192R polymorphism were found between patients and controls. The Q allele was more frequent in the patient group than in controls, while the R allele was more frequent in the control group. No significant differences were found in the L55M polymorphism. Additionally, there were no significant differences in L and M allele frequencies. We conclude that the R allele may protect against renal cell carcinoma.     

Brain mast cells and therapeutic potential of vasoactive intestinal peptide in a Parkinson's disease model in rats: brain microdialysis, behavior, and microscopy

In the present study, the effect of systemically administered vasoactive intestinal peptide (VIP) (25 ng/kg i.p.) was investigated on drug-induced rotational behavior, extra-cellular dopamine levels and histology of corpus striatum in a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease. After 15 days of 6-OHDA lesion, apomorphine-induced (0.05 mg/kg s.c.) rotational behavior of the animals significantly increased and extra-cellular dopamine levels of corpus striatum were significantly reduced. VIP reversed the rotational deficits but did not alter the decrease in striatal dopamine levels. On the other hand, histological data indicate that VIP significantly reduced neuronal death and demyelination. Electron microscopic appearance of mast cells showed ultra-structural variety between VIP-treated and 6-OHDA lesioned groups. VIP activates mast cells without any evidence of typical exocytosis, and possibly mast cells could participate in neuroprotection. Our results suggest that systemically administered VIP can attenuate the motor response changes, neuronal cell death, and myelin sheet loss characteristically associated with 12 microg 6-OHDA administration into the rat striatum. Brain mast cells seem to participate in neuronal protection. Possibly, protective cues could be produced by brain mast cells.     

Bos taurus and Bos indicus (Sahiwal) calves respond differently to infection with Theileria annulata and produce markedly different levels of acute phase proteins

Disease-resistant livestock could provide a potentially sustainable and environmentally sound method of controlling tick and tick-borne diseases of livestock in the developing world. Advances in the knowledge and science of genomics open up opportunities to identify selectable genes controlling disease resistance but first, breeds and individuals with distinguishable phenotypes need to be identified. The Bos indicus breed, Sahiwal, has been exploited in dairy breeding programmes, because it is resistant to ticks and has relatively good performance characteristics compared to other indigenous cattle breeds of tropical regions. The analyses reported here show that Sahiwal calves were also more resistant than European Bos taurus (Holstein) dairy breed calves to tick-borne tropical theileriosis (Theileria annulata infection). Following experimental infection with T. annulata sporozoites, a group of Sahiwal calves all survived without treatment, with significantly lower maximum temperatures (P<0.01) and lower rates of parasite multiplication (P<0.05) than a group of Holstein calves, which all had severe responses. Although the Sahiwals became as anaemic as the Holsteins, other measures of pathology, including enlargement of the draining lymph node and the acute phase proteins, alpha1 acid glycoprotein and haptoglobin, were significantly less in the Sahiwals than in the Holsteins (P<0.05). Additionally, the Sahiwals had significantly lower resting levels of alpha1 acid glycoprotein than the Holsteins (P<0.05). Production of a third acute phase proteins, serum amyloid A, had very similar kinetics in both breeds. Acute phase proteins are produced in response to systemic release of the kinds of pro-inflammatory cytokines that are thought to be responsible for the pyrexic, cachectic and anorexic responses characteristic of tropical theileriosis. The prolonged production of alpha1 acid glycoprotein in the Holsteins is indicative of chronic production of circulating pro-inflammatory cytokines. In contrast, Sahiwals appear able to overcome infection with T. annulata as well as limit pathology by preventing the over-stimulation of pathways involving these cytokines.     

Fine needle aspiration biopsy of the parotid gland. Diagnostic problems and 2 uncommon cases

OBJECTIVE: To describe the diagnostic problems and present our findings in 2 uncommon tumors, malignant myoepithelioma and small cell undifferentiated carcinoma, by examining fine needle aspiration (FNA) biopsies of parotid gland masses. STUDY DESIGN: The study group consisted of 34 females and 41 males 12-80 years old, with an average of 44. Excluding inflammatory results, all adequate aspirates were confirmed histologically to determine the correlation. RESULTS: Sensitivity of FNA cytology was 91%, with specificity of 98%. We encountered some difficulties, and therefore misdiagnoses, in evaluating specific neoplasms, such as adenoid cystic carcinoma and Warthin's tumor, which have well-established cytologic diagnostic criteria. Two cases of uncommon neoplasms of salivary glands, small cell undifferentiated carcinoma and malignant myoepithelioma, were cytologically found to be malignant but not further classified. In addition, tuberculous parotitis, with its well-defined features, should to be referred since unnecessary surgery can be avoided by using FNA cytology. CONCLUSION: FNA is a sensitive and specific diagnostic tool for parotid gland masses. However, specific classification of neoplasms may sometimes be difficult. Pathologists should be aware of specific entities, such as malignant myoepithelioma, when evaluating high grade neoplasms.     

Non-lethal Hallermann-Streiff syndrome with bone fracture: report of a case

The Hallermann-Streiff syndrome is characterized by bird-like face, micropthalmia, cataracts, micrognathia, beaked nose, abnormal dentition, hypotrichosis, cutaneous atrophy and proportional small stature. We present a 35-day-old patient with the classical signs except cutaneous atrophy, additionally he had a healing fracture at the proximal part of the left radius.