Altered acceptability of and preference for sugar solutions by diabetic rats is normalized by high-fat diet

Two experiments examined the ingestive responses of streptozotocin-diabetic rats fed low-fat or high-fat diets to glucose, fructose, sucrose and maltose solutions in brief (30 min) intake tests. In Experiment 1, one-bottle acceptability tests were used whereas two-bottle preference tests were used in Experiment 2. Three main findings resulted from these studies. Firstly, diabetic rats fed the low-fat diet displayed a reduced acceptance of and preference for all concentrated sugar solutions. Secondly, glucose consumption patterns of diabetic rats fed the low-fat diet were distinctly different from their responses to the other sugars. Thirdly feeding high-fat diets, either high or low in carbohydrate, normalized the responses of diabetic rats to the sugar solutions. The results suggest that feeding high-fat diets to diabetic rats normalizes their responses to sugar solutions because of reductions in hunger and thirst associated with the provision of a utilizable source of calories and an improvement in body fluid balance.     

Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo.

Killer lymphocytes play a major role in host defense against tumors and infectious diseases. Previously, we reported that delta-9-tetrahydrocannabinol (THC) and II-hydroxy-delta-9-tetrahydrocannabinol (II-hydroxy-THC) suppressed the cytolytic activity of cultured natural killer (NK) cells. Also, we showed that the drugs appeared to be affecting a stage in the killing process subsequent to the binding of the killer cell to the target cell. In the present report, we have extended these studies to an examination of the effect of cannabinoids on the activity of cytotoxic T lymphocytes (CTLs). The cytolytic activity of CTLs generated by cocultivation with either allospecific stimulators or TNP-modified-self stimulators were suppressed by both THC and II-hydroxy-THC treatment. Allospecific CTLs generated in vivo were also inhibited by an in vitro exposure to either THC or II-hydroxy-THC, and the sensitivity of these cells to drug effects appeared to be greater than the sensitivity of the in vitro generated CTLs. Suppression of cytolytic function by THC and II-hydroxy-THC was maximal after a 4-h drug treatment, suggesting that the drug effects were inducible and therefore required a finite period of time to develop maximally. As seen in previous studies involving NK cells, drug treatment of mature CTLs appears to have little effect on the binding capacity of these cells for the target. However, the maximal killing capacity of the cells and the frequency of CTLs were significantly reduced by drug treatment. In addition to suppressing the cytolytic activity of mature effector CTLs, we also show that drug treatment inhibits both the proliferation of lymphocytes responding to an allogeneic stimulus and the maturation of these lymphocytes to mature CTLs. Similarly, CTL activity developing in vivo could be inhibited by THC injection. These results suggest that CTLs are inhibited by cannabinoids by at least two mechanisms. First, the cytolytic activity of mature killers is suppressed at some point beyond the binding to the target cell. Second, the cannabinoids appear to suppress the normal development of these mature effector cells from less mature precursor cells.     

Glucocorticoid effects on phenylethanolamine N-methyltransferase (PNMT) in explants of embryonic rat medulla oblongata

Although glucocorticoid hormones have important roles in the development of neurotransmitter systems in cells derived from the neural crest, it is not known whether they have parallel effects on neuronal development in the brain. To address this issue, we have established an in vitro system of fetal medulla oblongata (MO) to follow development of the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT). Embryonic MO was explanted from E13 or E18 embryos and maintained for up to 3 weeks. Successful culture of adrenergic neurons was possible only in explants taken from young embryos, since E18 explants failed to develop. In E13 explants, immunoreactivity to both PNMT and tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis, was observed. PNMT catalytic activity which was barely detectable at the time of explanation increased markedly during the first week in vitro. To study the effects of glucocorticoids on PNMT development in central neurons, MO explants were grown in glucocorticoid deficient medium in which rat serum from adrenalectomized rats was substituted for human placental serum. Addition of natural glucocorticoids, cortisol or corticosterone, or the mineralcorticoid, deoxycorticosterone, during the third culture week had no effect on PNMT activity. Dexamethasone (DEX), a synthetic glucocorticoid, also had no effect on PNMT during the first or second weeks in culture. However, addition of DEX during the third culture week resulted in a doubling of PNMT activity. However, attempts to block the DEX effect during the third week or to block the increase in PNMT activity during the first week in control cultures with the glucocorticoid receptor antagonist, dexamethasone 21-mesylate, were unsuccessful. These results suggest that PNMT in central neurons does not require glucocorticoids for ontogeny during the embryonic period. This is in contrast to PNMT in adrenal medulla which requires glucocorticoids for normal development during both the embryonic and postnatal periods. More generally, these studies suggest that development of the same neurotransmitter phenotype in brain and periphery may be differentially regulated.     

Geriatric diabetic nephropathy: an analysis of renal referral in patients age 60 or older

We report a series of 33 consecutive hospitalized geriatric diabetic patients who were referred for evaluation of diabetic nephropathy, defined as proteinuria greater than or equal to 1 g/d (1,000 mg/24 h) or a serum creatinine concentration greater than or equal to 177 mumol/d (greater than or equal to 2 mg/dL). The study population was 60 years old or older (mean age, 68 +/- 6 years), was comprised mainly of women (24 of 33, 72.7%), and was predominantly black (25 of 33, 75.8%). All patients had type II diabetes. A family history of diabetes in parent or sibling was elicited in 24 (72.7%) patients. There were eight patients undergoing maintenance hemodialysis and 25 with less severe nephropathy (mean proteinuria, 2.7 g/d [2,700 mg/24 h]; mean creatinine clearance, 0.57 mL-s [34 mL/min]). Cardiac disorders were noted in the majority of patients: congestive failure in 20 (60.6%), myocardial infarction in eight (24.2%), and active angina in five (15.2%). Other comorbid diseases were present in both hemodialysis patients and the subset of nondialyzed azotemic-proteinuric patients, and consisted of peripheral neuropathy in 31 (93.9%), gastroparesis in 16 (48.5%), retinopathy in 28 (84.8%), and legal blindness in 11 (33%). We conclude that geriatric diabetic nephropathy in type II diabetes is similar in presentation and severity of comorbid extrarenal complications to the syndrome described in younger adults. This inference must be tempered by both the small size and the limitation imposed by the demographics of the study population, which is predominantly composed of black patients receiving treatment at inner city hospitals.     

Clinical findings and common symptoms in retinitis pigmentosa

Data analysis was performed in a prospective study of clinical symptoms and findings in 500 patients with retinitis pigmentosa. The symptoms and findings in these patients met the usual definitions of the disease. At initial examination the patients were questioned in a standardized manner; symptoms and associated health problems were reviewed. Some patients were unable to answer all of the questions. Of the patients 274 (55%) were men and 226 (45%) were women, with a race distribution of 21 (4%) black, 47 (9%) Hispanic, 26 (5%) Oriental, three (1%) American Indian, and 403 (81%) white. Sixty-nine patients reported no symptoms of night blindness and 116 patients claimed no visual field changes; 90 stated that they saw better at dusk. The most common problem noted by 263 (53.3%) was headaches, 31 on a daily basis, 42 at least weekly, 124 infrequently, and the remainder nonspecifically. Numbness or tingling, mainly in extremities, was reported by 99 patients. The second most common problem affecting 170 patients (34.6%) was light flashes; since eight patients had retinal detachments, light flashes cannot be totally discounted. Of 143 patients who had been pregnant, 14 had visual changes.     

The tarsal pillar technique for narrowing and maintenance of the interpalpebral fissure.

We describe a tarsorrhaphy technique whereby an ipsilateral upper-eyelid tarsal pillar is sutured to a corresponding lower-eyelid recipient site. This technique allows maintenance of a narrowed interpalpebral fissure indefinitely, yet is easy to reverse without incurring lid-margin damage. Additionally, the procedure can be adjusted postoperatively to either narrow or widen the initial surgical result. We report our combined surgical experience in 35 consecutive procedures using this technique to treat eyes with exposure-related keratopathy of varied etiology, including facial nerve palsies, combined facial nerve palsy and trigeminal neuropathy with an anesthetic cornea, Graves' disease, congenital craniofacial anomalies, and severe keratitis sicca syndrome. The procedure was successful in improving exposure keratopathy symptoms in all 35 cases. Complications, reflecting the authors' learning curve with this new procedure, included intermarginal pyogenic granulomas, stretching of the tarsal pillar, minor lower-eyelid-margin eversion, and tarsal pillar dehiscence.     

Contrasting Effects of thc on Adult Murine Lymph Node and Spleen Cell Populations Stimulated with Mitogen or Anti-CD3 Antibody

Marijuana, and specifically its psychoactive component, THC, can up or down regulate lymphocyte proliferation in murine spleen cells depending in part on the method used to stimulate the cells. This study identifies a difference in THC induced disregulation using cells derived from two different secondary lymphoid organs, the spleen and the lymph node. It was found that THC treatment of mitogen (concanavalin A or phytohemagglutinin) stimulated cells derived from either organ resulted in suppression of the proliferative response. In contrast, spleen cells stimulated with anti-CD3 antibody and treated with low doses of THC displayed an enhanced proliferation whereas the response in lymph nodes did not change. The cell type involved with this THC immunoenhancement in spleen cells was found to be the Ly2 cell. Further differences in the THC modulation of Ly2 spleen cells as compared to lymph node cells were noted following stimulation with PHA. Proliferation of Ly2 cells of splenic origin was inhibited with low doses of THC whereas the Ly2 cells of lymph node origin were more resistant to this drug induced suppression. This study, therefore, demonstrates differences in the immunomodulatory capability of THC dependent upon the organ source of the lymphocytes.     

Radiographic manifestations of bronchiolitis obliterans with organizing pneumonia vs usual interstitial pneumonia

The radiographic findings in 24 cases of bronchiolitis obliterans with organizing pneumonia and 16 cases of usual interstitial pneumonia were reviewed and compared. Some cases of bronchiolitis obliterans with organizing pneumonia have been mistaken for usual interstitial pneumonia, although the two diseases have distinct pathologic findings. Clinically, the diseases often have different manifestations. Bronchiolitis obliterans with organizing pneumonia has a better prognosis and often responds well to steroids. This study shows that the radiologic findings of bronchiolitis obliterans include alveolar opacities without lung-volume loss. Patients with usual interstitial pneumonia, however, have bilateral diffuse interstitial opacities with occasional honeycomb changes, and there is loss of lung volume in most patients. These findings suggest that the chest radiograph can aid in distinguishing the two diseases.