Effects of pravastatin on progression of glucose intolerance and cardiovascular remodeling in a type II diabetes model

OBJECTIVES: We examined the effects of early treatment with a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on the progression of glucose intolerance and cardiovascular remodeling in a model of spontaneously developing type II diabetes mellitus (DM), the Otsuka Long-Evans Tokushima Fatty (OLETF) rats. BACKGROUND: Clinical trials showed that pravastatin prevented new-onset DM in hypercholesterolemic patients, and that it was effective in prevention of cardiovascular events in diabetics. METHODS: The OLETF rats were treated with pravastatin (100 mg/kg/day) from 5 weeks of age and compared with age-matched untreated OLETF rats and normal Long-Evans Tokushima Otsuka (LETO) rats on serial oral glucose tolerance tests (OGTT) and Doppler echocardiography and on histopathological/biochemical analyses of the heart at 30 weeks. RESULTS: The OGTT revealed that 40% and 89% of untreated OLETF rats were diabetic at 20 and 30 weeks, respectively, but 0% and only 30%, respectively, were diabetic in the treated OLETF. Left ventricular diastolic function was found impaired from 20 weeks in untreated OLETF but remained normal in the treated-OLETF. The wall-to-lumen ratio and perivascular fibrosis of coronary arteries were increased in untreated-OLETF but were limited in the treated-OLETF at 30 weeks. Moreover, cardiac expressions of a fibrogenic growth factor, transforming growth factor-beta1 (TGF-beta1), and a proinflammatory chemokine, monocyte chemoattractant protein-1 (MCP-1), were increased in untreated-OLETF. However, in the treated-OLETF, overexpressions of TGF-beta1 and MCP-1 were attenuated, which was associated with overexpression of endothelial nitric oxide synthase (eNOS) (2.5-fold of control LETO). CONCLUSIONS: Early pravastatin treatment prevented cardiovascular remodeling in the spontaneous DM model by retarding the progression of glucose intolerance, overexpressing cardiac eNOS, and inhibiting overexpressions of fibrogenic/proinflammatory cytokines.     

Lacrimal gland accumulation of 67Ga-citrate in patients with Sjögren's syndrome

The extent of ⁶⁷Ga accumulation in the two lacrimal glands in patients with keratoconjunctivitis sicca (KCS) of Sjögren's syndrome was studied. Of the two main groups one consisted of 69 subjects without ophthalmic complaints (control group), the other consisted of 26 patients with KCS of Sjögren's syndrome. Of the 26 patients with KCS, 7 had been diagnosed as probable KCS (probable sub-group) and the other 19 had been diagnosed definite KCS (definite sub-group). About 3 mCi (111 MBq) ⁶⁷Ga-citrate was injected IV into each subject and this was followed by scintigraphy at 24, 48, and 72 h after the injection of ⁶⁷Ga. A positive finding in the lacrimal gland was noted in 64 of 69 subjects (92.7%) in the control group and in 7 of 7 patients (92.7%) in the control group and in 7 of 7 patients (100%) with probable KCS. Three of 19 patients with definite KCS (15.7%) showed positive findings under scintigraphy. When the scintigraphic finding in the lacrimal gland is not positive in patients with suspected KCS of Sjögren's syndrome, they can then be diagnosed with little risk as definite KCS cases. Shirmer's test was performed on subjects in the probable and definite groups. There was statistical significance between the positive and equivocal or negative scintigraphic finding and Schirmer's values. These results suggest a correlation between gallium accumulation in the lacrimal gland and the tear production.     

Analysis of beta3 adrenergic receptor gene polymorphism using noninvasive samples obtained at scheduled infant health checkups.

Obesity is a risk factor for life-style-related diseases, and is based on three factors: genetic, environmental, and life-style. In adults, it is difficult to achieve and maintain normal body weight, so it is more effective to intervene from infancy to establish weight control. Legally required health checkups in infants of 18 and 36 months present important opportunities for obesity prevention. We consider genetic analysis to be a very important factor for obesity prevention in infancy. However, since health checkups don’t involve the collection of blood, genetic analysis is considered difficult. In this study, we attempted the typing of beta3 adrenergic receptor gene polymorphism as a genetic factor from non-invasively obtained samples, buccal mucosa, hair and cerumen in 96 infants at their 18- and 36-month health checkups. Sampling buccal mucosa, hair and cerumen instead of blood caused almost no anxiety to the child or parent, so 94.1% cooperation with sampling was obtained. From buccal mucosa, about 76% of the samples could be used for the typing of polymorphism (81% by enzyme method, 59% by kit method). From hair, about 44% of the samples permitted typing of polymorphism, but from cerumen only about 4% of the samples could be used. Results from buccal mucosa and hair typed about 90% of infant polymorphism. These results suggest that this method would be practical at periodic health checkups, and would probably be applicable to mass screenings for genetic factor analysis for other diseases.