Cutaneous afferent activity in the median nerve during grasping in the primate

Neural activity was recorded from the median nerve of a monkey during grasping and lifting, using a chronically implanted cuff electrode. At the onset of lifting, there was an initial dynamic response during which the intensity of the neural signal increased rapidly. This neural response attained its peak value well before the displacement, the load force or the grip force. The time course and peak of the rectified, integrated neurogram were best correlated with the rate of change of grip force. The neural activity declined exponentially to a steady value following the initial peak. During steady holding the mean amplitude of the neurogram was best correlated with the mean grip force. At the end of the holding phase there was a short burst of neural activity as the monkey relaxed the grip force and released the object. During some blocks of trials pulse perturbations were applied to the object. When the monkey did not increase the grip force in advance of the perturbation, the perturbation produced a relatively large displacement of the object and a burst of neural activity whose onset coincided with the onset of displacement. When the monkey anticipated the perturbation by increasing the grip force during the holding period preceding the perturbation, the perturbation produced a relatively small displacement and relatively little increase in neural activity.     

Evidence for a distinct nigropallidal dopaminergic projection in the squirrel monkey

Injections of the retrograde fluorescent tracer fast blue in the striatum (STR) and nuclear yellow in the internal segment of the globus pallidus (GPi) in the squirrel monkey (Saimiri sciureus) revealed a nigropallidal projection whose cellular origin was largely distinct from that of the nigrostriatal pathway. Neurons containing the tracer injected in GPi were scattered throughout the substantia nigra-ventral tegmental area complex where they formed approximately 20-25% of the total number of retrogradely labeled cells. Only about 5-10% of all positive neurons were double-labeled after STR-GPi injections. In experiments combining the use of the fluorescent tracer propidium iodide with immunofluorescence, the majority of neurons projecting to GPi displayed tyrosine hydroxylase immunoreactivity. Hence, in addition to their important role at striatal level, midbrain dopaminergic neurons may influence directly the output neurons of the basal ganglia at pallidal level in primates.     

Dissociation of GFAP intermediate filaments in EAE: observations in the lumbar spinal cord

Acute experimental allergic encephalomyelitis (EAE) in the Lewis rat is a cell-mediated autoimmune disease of central nervous system myelin. The lesion has been characterized by breakdown of the blood-brain barrier, edema, and periventricular infiltration of macrophages and lymphocytes. At the early stage of the disease, the astrocytes show a marked increase in immunostaining for glial fibrillary acidic protein (GFAP). A corresponding increase in GFAP content, however, cannot be demonstrated. Electron microscopic examination of the early lesion shows a typical reactive astrocytic response expressed by an enlarged watery cytoplasm, particularly at the level of the processes surrounding neurons and blood vessels and in the neuropil itself. The astroglial processes contain numerous glycogen particles (aggregates and single particles). Glial filaments are also conspicuous and are arranged in small bundles or loose thin filaments adjacent to the bundles. The glial filaments that normally appear as tight bundles have expanded and appear less dense. We suggest that the increase in GFAP immunostaining of the astrocytes in the early lesion is due in part to edema, which causes dissociation of the filaments and thereby exposes more antigenic sites to the antibodies.     

Thyroid hormones modulate thyrotropin-releasing hormone biosynthesis in tissues outside the hypothalamic-pituitary axis of male rats

In the present study we have examined the in vivo effects of thyroid hormone and TRH on secretory tissue concentrations of TRH and TRH-Gly (pGlu-His-Pro-Gly), a TRH precursor. Within secretory granules, TRH-Gly is converted to TRH through alpha-amidation of the C-terminal proline residue, using Gly as the NH2 donor. Using specific RIA, we measured the TRH-Gly immunoreactivity (TRH-Gly-IR) and TRH-IR concentrations in tissues from the reproductive and gastrointestinal systems, adrenals, and other internal organs in euthyroid, hypothyroid, and T4-treated 250-g Sprague-Dawley male rats. TRH-Gly-IR concentrations were more than 2-fold higher than TRH-IR concentrations within the adrenal, pancreas, bowel, and stomach at the time of death. Untreated hypothyroidism and exogenous TRH significantly increased adrenal TRH-Gly-IR levels. Pancreatic TRH-Gly levels increased about 2-fold in hypothyroid rats. Incubation at 60 C significantly increased TRH-Gly-IR levels in the pancreas, adrenal, bowel, stomach, and epididymis by 14-, 3-, 6-, 6-, and 6-fold, respectively. Also after 60 C incubation increases in the TRH-Gly-IR/TRH-IR ratio of 2.7-, 4-, and 1.7-fold were observed in the pancreas, epididymis, and bowel, respectively. Pooled tissue extracts were fractionated by cation exchange and reverse phase HPLC for characterization of TRH-Gly-IR. Both chromatographic methods revealed a major peak of TRH-Gly-IR coeluting with synthetic TRH-Gly. Incubation at 60 C caused 13.5-, 4.1-, 1.5-, and 5-fold increments in the TRH-Gly-IR for adrenal, pancreas, prostate, and thyroid, respectively, compared to the immediately extracted control aliquots. Cation exchange and reverse phase HPLC also revealed production of higher mol wt TRH precursor peptides after incubation at 60 C for 4 or 20 h. Only the TRH-Gly-IR peak coeluting with pGlu-His-Pro-Gly was converted into TRH by rat brain alpha-amidating enzyme. The data suggest that biosynthesis of TRH occurs in rat extrahypothalamic tissues and may be modulated by thyroid status, iv TRH, and selective thermal inactivation of enzymes that convert prepro-TRH to TRH.     

A preliminary report of the short-term effect of carbonated beverage consumption on calcium metabolism in normal women

A variety of nutritional factors influence the bioavailability of calcium and increase a woman's risk of osteoporosis. Eight healthy women completed an 8-week metabolic study designed to investigate the effect of nonalcoholic carbonated beverage consumption on calcium metabolism. Compared with women receiving a control diet, women consuming a diet high in nonalcoholic carbonated beverages demonstrated similar mean serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 1,25-dihydroxyvitamin D3, and osteocalcin. Twenty-four-hour urine volume, creatinine clearance, calcium-creatinine ratio, and phosphorus-creatinine ratio were similar during consumption of the diet high in nonalcoholic carbonated beverages and the control diet. Twenty-four-hour cyclic adenosine monophosphate-creatinine ratio was significantly lower in women consuming the diet high in nonalcoholic carbonated beverage compared with women receiving the control diet (342 +/- 27.4 nmol/mmol vs 409 +/- 22.1 nmol/mmol). Consumption of a diet high in nonalcoholic carbonated beverages on a short-term basis does not appear to affect adversely the serum or urinary markers of calcium metabolism.     

Traumatic Injury of the Superior Mesenteric Vein: Ligate,Repair or Shunt?

Abstract We report a case of SMV injury in a critically ill patient. The patient was a 19-year-old woman involved in a motor vehicle collision. Her injuries included grade II splenic and renal lacerations, devascularized and lacerated right and transverse colon, a transected transverse mesocolon, a massive shear injury of her abdominal wall, and two partial SMV transections. At initial damage control laparotomy, the SMV was ligated, the devascularized bowel resected and a temporary abdominal closure applied. At re-operation, a mesocaval shunt using saphenous vein was employed. The shunt failed and the patient required a saphenous vein jump graft. Although visceral vascular injuries are rare, ligation of the SMV in a damage control situation is acceptable. This case study is the first to discuss appropriate treatment when interruption to a patient's collateral visceral venous drainage limits the surgeon’s ability to ligate. In these situations, bypass shunts may be successful.     

Modification to improve efficiency of sampling schedules for BA/BE testing of FDC anti-tuberculosis drugs.

SETTING: The assessment of rifampicin (RMP) containing fixed-dose combination (FDC) formulations using in vivo bioequivalence testing is widely accepted. It would be advantageous for both the drug regulatory authorities and drug manufacturers, for optimum minimum blood testing time intervals that encompass all anti-tuberculosis active constituents in the FDC to be established. OBJECTIVE: To determine the optimum blood sampling schedule for testing novel FDC anti-tuberculosis drugs, isoniazid, RMP, pyrazinamide and ethambutol DESIGN: The results of 12 different single-dose, two-way cross-over designs are presented. The studies determined the bioavailability and bioequivalence of RMP-containing FDCs, and conformed with the requirements of the South African national drug regulatory authority for each of the active constituents. RESULTS: The pharmacokinetic parameters to determine bioavailability and the Hauschke method to determine bioequivalence revealed that a six-point time protocol, namely 0, 1, 2, 4, 6 and 8 h, provides a good approximation of the area under the curve, and that an 11-point time protocol of 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 h provided information comparable to the conventional 15 time-points for FDCs containing up to four drugs. CONCLUSION: The findings provide concrete economic benefit and convenience for quality assurance testing of existing and novel FDCs.