A novel cobiotic-based preventive approach against high-fat diet-induced adiposity, nonalcoholic fatty liver and gut derangement in mice.

BACKGROUND: High-fat diets (HFDs) induce systemic inflammation, gut microbial derangements and disturb metabolic homeostasis, resulting in weight gain, insulin resistance and nonalcoholic fatty liver (NAFL). Numerous antioxidants and prebiotic/probiotics per se may prevent HFD-associated comorbidities, but there are no reports related to their combination. OBJECTIVE: In the present study, we aim to evaluate a cobiotic combination of lycopene (antioxidant) and isomalto-oligosaccharides (IMOs, a prebiotic) for prevention of HFD-induced alterations. DESIGN: Male Swiss albino mice were fed either normal pellet diet (NPD) or HFD and lycopene (5 and 10 mg kg(-1)), IMOs (0.5 and 1 g kg(-1)) or their combination for 12 weeks. Systemic adiposity, glucose tolerance, insulin sensitivity, feeding regulators in hypothalamus, hepatosteatosis and liver inflammation, cecal short chain fatty acids (SCFAs), serum inflammatory cytokines, gut morphology and alterations in selected gut microbes were studied. RESULTS: Lycopene, IMOs and their combination prevented weight gain, adiposity, improved adipose tissue fat mobilization and reduced insulin resistance. Hypothalamic orexigenic and anorectic genes have also been modulated by these treatments. Dietary interventions prevented NAFL-like symptoms and improved glucose homeostasis. Improvement in selected gut microbial abundance and SCFA concentration along with reduced systemic inflammation, metabolic endotoxemia and improved ileal and colonic health were observed in mice supplemented with lycopene, IMOs and their combination. Interestingly, cobiotic combination synergistically improved many of the HFD-induced alterations. CONCLUSION: The present work provide evidence that new approach based on cobiotic combination (antioxidant plus prebiotic) can be employed to develop novel class of functional foods for their application against HFD-associated pathological complications.

Diabetes mellitus and optic atrophy in two siblings: a report on a new association and a review of the literature.

Two siblings with diabetes mellitus and optic atrophy (Wolfram syndrome) are described. As often noted, they also had atonic urinary bladders. Only one of the siblings had some impairment of hearing. Other findings not previously reported that appeared in each subject were esophageal dysphagia and vertigo. An autopsy in one revealed brain stem hypoplasia and thinning and flattening of the optic nerves with atrophy of the lateral geniculate bodies.

Severe hypophosphatemia. Pathophysiologic implications, clinical presentations, and treatment.

We conducted this review to heighten the awareness and describe pathologic manifestations of hypophosphatemia. We present 3 cases of varied manifestations of hypophosphatemia where recognition was delayed. In certain settings, severe hypophosphatemia has significant morbidity and potential mortality. Appreciation of the pathophysiologic basis for organ dysfunction in severe hypophosphatemia should result in early recognition and treatment. We reviewed the English-language literature for reported cases and research studies dealing with pathophysiologic mechanisms subserving clinical manifestations. We observed that depletion of adenosine triphosphate (ATP) would explain most of the derangement noted in cellular functions. Phosphate plays a key role in the delivery of oxygen to the tissue. Lack of phosphate, therefore, leads to tissue hypoxia and hence disruption of cellular function. Severe hypophosphatemia becomes clinically significant when there is underlying phosphate depletion. Otherwise, short-term acute hypophosphatemia is not usually associated with any specific disorder. Chronic hypophosphatemia, on the other hand, results in hematologic, neuromuscular, and cardiovascular dysfunction, and unless corrected, the consequences can be grave. Most of the time hypophosphatemia results from renal loss of phosphate, diagnosed by a fractional secretion of phosphate > 5%. It is hard to provide precise estimates of how many patients are seen with hypophosphatemia annually at academic medical centers. This is complicated by use of chemistry panels that do not measure inorganic phosphate unless specifically ordered. This often leads to delay in correct diagnosis, and, therefore, additional delay in providing appropriate management. A high index of suspicion alone avoids the unnecessary withholding of treatment that can be life saving.

Hyperosmolar hyperglycemic nonketotic syndrome. Report of 22 cases and brief review.

In a series of 22 patients with the hyperosmolar hyperglycemic nonketotic syndrome managed during a five-year period in a community hospital setting, 21 patients were known to be diabetic and only six patients were in coma. The overall mortality was 36.3 percent, and seven of the eight deaths were explained by associated nonmetabolic causes. In this study, hyperosmolarity was not related to coma or to final outcome of treatment. Patients were managed with relatively small amounts of fluid, and the type of fluid used did not influence the final outcome.

Graves' ophthalmopathy. An unusual course.

A patient with an unusual course of Graves' ophthalmopathy is presented; serial computed tomographic scanning of the orbits was used to follow the course of the eye disease. Right-sided unilateral ophthalmopathy first developed two years after thyroid ablation with radioactive iodine and was followed by complete resolution two years later. The remission of this patient's eye disease was short-lived; within eight months, unilateral ophthalmopathy affected the left eye, and ophthalmopathy recurred in the right eye a few months later. Current hypotheses do not readily explain the course of this patient's ophthalmopathy.

Electrocardiographic finding simulating acute myocardial infarction in a compound metabolic aberration.

A patient with hypokalemic metabolic alkalosis, hypophosphatemia, and hypomagnesemia/hypocalcemia is described. Electrocardiography demonstrated the pattern of acute anterior myocardial infarction. Further evaluation revealed that the patient had not actually had the acute myocardial infarction and that the electrocardiographic change was a mere simulation. The possible role of hypomagnesemia in the pathogenesis of the electrocardiographic change and the interrelation between the metabolic disturbances noted are discussed.

Lymphocytic interstitial pneumonitis in autoimmune thyroid disease.

Four patients are described who were found to have autoimmune thyroid disease associated with lymphocytic interstitial pneumonitis. The patients were not receiving any medications known to cause lymphocytic interstitial pneumonitis. Their response to steroid therapy and the relapse of their clinical symptoms after steroid withdrawal support an underlying immunologic dysfunction. It is proposed that lymphocytic interstitial pneumonitis may be yet another manifestation of immune dysfunction in autoimmune thyroid disease.

Adrenocortical function in experimental protein malnutrition.

Adrenocorticoid activity was investigated in experimentally induced protein malnutrition in Rhesus monkeys. Control studies were carried out in the same animals before inducing protein malnutrition. Plasma cortisol levels were elevated in the protein malnourished state. There was a total abolition of the diurnal rhythm of cortisol secretion. Fasting hypoglycemia was also observed in the protein malnourished state. It is concluded that increased adrenocorticoid activity and sustained steroidogenesis result from protein deficiency. Hypoglycemia may be an important stimulus, in addition to the metabolic stress imposed by the protein deprivation. The recognition of increased adrenocorticoid activity is important in a protein-deficient host, since the defense against infections might be impaired in such a situation.

Failure to obtain follow-up testing for gestational diabetic patients in a rural population.

OBJECTIVE: To determine physician and patient compliance rates for diabetes testing in patients with previous gestational diabetes. METHODS: Questionnaires regarding follow-up testing and personal health history were sent to 66 patients with previous gestational diabetes who did not have diabetes when they participated in a follow-up study conducted 5 years earlier. A 2-hour glucose tolerance test (GTT) was offered to those whose last test was done more than 1 year previously. RESULTS: All 66 individuals returned the questionnaire and 20 (30.3%) reported having received a yearly 2-hour GTT. Of the remaining 46, 19 had been tested at least once in the previous 5 years, but 27 had not been tested. Of the patients who had been tested at least once in the 5-year period, their physicians initiated testing 61.5% of the time and the patients initiated the remainder. There were no significant differences between physician specialty and rate or appropriateness of the testing. Of 39 individuals who had been tested at least once in the 5-year period, eight had diabetes and four were glucose intolerant. Of 12 individuals who had not been tested in the past year and agreed to be tested in 1995, four had diabetes and two had glucose intolerance. CONCLUSION: Although physicians and their gestational diabetic patients knew the risks of diabetes development, compliance with follow-up testing was poor and the risk of developing diabetes high.

Usefulness of MC-540 fluorescent dye as probe versus scanning electron microscopy for assessing membrane changes.

The effect of primaquine enantiomers on cell membranes of glucose-6-phosphate (G-6PD)-deficient erythrocytes was studied in vitro. Staining with merocyanine (Mc-540) showed that exposure to primaquine enantiomers produces significant fluorescence in G-6PD-deficient erythrocytes, indicating marked drug-induced alterations in membrane fluidity. Scanning electron microscopy (SEM) studies confirmed that primaquine enantiomers altered membrane morphology (by producing stomatocytes) in both normal and G-6PD-deficient cells. The concentration-dependent effect, however, was more pronounced with MC-540, a lipophylic dye, than with SEM (an expensive technique).

Hyperparathyroid crisis manifesting as respiratory and heart failure.

OBJECTIVE: To describe a case of hyperparathyroid crisis manifesting as respiratory failure and congestive heart failure and to emphasize the implications of hypercalcemia and hypophosphatemia in this setting. METHODS: A case report and a review of the pertinent literature are presented. RESULTS: A 71-year-old man was transferred to our care because of respiratory failure and congestive heart failure. He had no change in cardiorespiratory status until the significance of hypercalcemia and hypophosphatemia was recognized and therapy was directed at correction of these abnormalities. Primary hyperparathyroidism was the cause of these electrolyte abnormalities. CONCLUSION: To our knowledge, hyperparathyroid crisis manifesting as respiratory insufficiency and congestive heart failure has not been described previously. Phosphate depletion may account for the neuromuscular features seen in hyperparathyroidism.

Gene therapy: a status report.

Gene therapy is a way to treat disease by transfer of genetic material into the cells of a diseased organism. Generally it is transferred in the form of one or few genes. There is a tremendous potential for application of this technique to the treatment of human hereditary diseases, particularly single gene disorders. Due to ethical and practical reasons, it is currently being used only as somatic cell therapy but it could be achieved by germline also. The major problem in gene therapy is achieving an efficient gene transfer and a persistent gene expression in appropriate somatic cells.