Clinical and nerve conduction study correlation in patients of diabetic neuropathy.

AIMS AND OBJECTIVES: 1) To study types of neuropathy in Type 2 diabetes. 2) To correlate clinical features of peripheral neuropathy with nerve conduction study in Type 2 diabetes. MATERIAL: A total of 50 diabetics, whose onset of diabetes after the age of 30 years were studied from Dr. D. Y. Patil hospital and research centre. Type 2 Diabetes mellitus with symptom suggestive of peripheral neuropathy were studied and included. Chronic alcoholic, peripheral neuropathy due to any other known cause were excluded. METHOD OF COLLECTION OF DATA: History of symptoms like paraesthesia like tingling sensation, burning feet, hyperaesthesia, foot ulcer, history of weakness and gait abnormality was noted. Complete central nervous system examination was performed to look for signs such as diminished ankle jerk, diminished power. Sensory examination for loss of light touch, superficial pain, temperature sense, vibration and joint position was done. Nerve conduction studies were performed using Clarity Octopus NCV/EMG machine. Written and informed consent from patient were taken. RESULTS: 1) 46 patients i.e. 92% presented with complaints of tingling sensation and 32 patients i.e. 64% had burning feet. 2) 29 patients i.e. 58% have diminished ankle jerk, 29 patients i.e. 58% have diminished or loss of vibration sense, in 21 patients i.e. 42% patients have diminished light touch and 20 patients i.e. 40% patients have loss of joint position senses. 3) NCV performed on 50 patients of diabetic neuropathy out of which all patients i.e. 100% had involvement of lower limb and only 24 patients i.e. 48% had involvement of upper limb also. 4) Involvement of tibial and sural nerve is more common i.e. 86% and 82% respectively. 5) 42 patients i.e. 84% found to have distal symmetrical polyneuropathy, 2 patients i.e. 4% had isolated tibial nerve involvement, 4 patients i.e. 8% had pure sensory sural nerve involvement, and only 1 patient each of isolated medial and plantar nerve involvement. CONCLUSION: Distal symmetrical polyneuropathy is most common form of diabetic neuropathy. Involvement of tibial and sural nerve is more common in diabetic neuropathy.

In utero ethanol exposure retards growth and alters morphology of cortical cultures: GM1 reverses effects.

Ethanol, a developmental neurotoxin, alters plasma membranes' physicochemical properties affecting embryogenesis, cell migration, differentiation, and synaptogenesis. In a previous study using a model for fetal alcohol effects, GM1 ganglioside treatment was shown to reduce ethanol-induced accumulation of endogenous GM1 and fatty acid ethyl esters in rat fetuses. The present study was initiated to define further the in utero effects of ethanol and the capacity of GM1 treatment to ameliorate such effects. Wistar dams were exposed to ethanol (intragastrically) on gestation day (GD) 7 and GD8 and GD13 and GD14. GM1 ganglioside (10 mg/kg, im) was given 24 hr before ethanol administration. Cortical cultures were derived from GD15 and GD20 fetuses. GM1, which is highly localized on the cellular plasma membrane outer surface of CNS cells, was used as a marker molecule to assess cell integrity. Cholera toxin/antitoxin/fluorescence immunohistochemistry was used to localize GM1. Results indicate that the brief in utero exposure to ethanol affected cell growth and morphology. A marked retardation of cell development and arborization was observed as early as 24 hr after plating. Ethanol-exposed cells evidenced considerably altered GM1 localization. Such alterations likely reflect losses of membrane integrity. These in utero ethanol-induced pathologies are remarkably diminished in cultures derived from ethanol-exposed fetuses of dams treated with GM1.

Antioxidant defense systems in the brains of type II diabetic mice.

The specific activities of superoxide dismutase, catalase, and glutathione S-transferase (mu subtype) were significantly lower in the brains of mice with type II diabetes than in the brains of control mice. On the other hand, the specific activity of glutathione peroxidase was unaltered. The concentration of vitamin E, but not that of total glutathione and ascorbate, was increased in the brains of the type II diabetic mice. The relative amount of polyunsaturated fatty acids (as determined with soybean lipoxygenase) was increased in whole brains and crude synaptosomal membranes of the type II diabetic mice. Endogenous levels of thiobarbituric acid-positive material were decreased in both whole brain homogenates and crude synaptosomal membranes of the db/db mice. Susceptibility of lipids within whole brain homogenates and crude synaptosomal membranes of mice with type II diabetes to peroxidation with iron/ascorbate was also markedly decreased compared with that of controls. Vitamin E is known to quench lipid peroxidation. Therefore, decreased lipid peroxidation in the type II mouse brain may be due to increased vitamin E content.

Reduction of fatty acid ethyl ester accumulation by ganglioside GM1 in rat fetus exposed to ethanol.

The biochemical mechanism of alcohol teratogenicity is not known. We have demonstrated that alcohol administration to pregnant rats during gestation days (GD) 6 and 7 and/or 13 and 14 leads to significant accumulation of ethyl esters of long chain fatty acids (FAEEs) in both maternal and fetal organs. This observation extends the report of Bearer et al. (Pediat Res 31: 492-495, 1992) who detected the presence of metabolites in maternal and fetal organs of pregnant C57B1/6J mice exposed to alcohol on GD 7 and/or GD 14. The ethyl esters of arachidonic, linoleic, oleic, stearic and palmitic acids were major metabolites detected in both maternal and fetal organs. It was also demonstrated that detectable levels of FAEEs remain 14 days (GD 20) after initial exposure to alcohol on GD 7. Ganglioside GM1 treatment 1 and 24 hr prior to alcohol exposure on both GD 7 and/or GD 14 reduced the accumulation of FAEEs. A similar regimen was shown to prevent development of tolerance to alcohol in the adult pups exposed to alcohol in utero in our previous studies. Thus, the ganglioside GM1 may have therapeutic value in reducing neurobehavioral effects of alcohol exposure in utero.

Ganglioside GM1 reduces fetal alcohol effects in rat pups exposed to ethanol in utero.

We have investigated the effect of in utero ethanol exposure and ganglioside GM1 pretreatment on the endogenous ganglioside profile of the rat fetal brain. Prenatal ethanol exposure on gestation day (GD) 7 and GD8 and/or GD13 and GD14 leads to a very significant increase in the ganglioside GM1 content in at least 50% of the pup brains when assayed on GD20. This treatment protocol also results in significant decrease in the content of polysialogangliosides GD1a, GT1b, and GQ1b. GM1 treatment of pregnant dams before ethanol administration prevented this alteration in pup brain ganglioside profile. Ganglioside GM1 pretreatment appears to block the cellular membrane changes associated with fetal alcohol effects and thereby minimizes alterations in brain maturation and associated behavioral dysfunction.

Monosialoganglioside (GM1) restores membrane fatty acid levels in ischemic tissue after cortical focal ischemia in rat.

Using a consistent, reproducible and reliable cortical focal ischemia in rat (permanent unilateral occlusion of the left middle cerebral artery & the ipsilateral common carotid artery [MCAo + CCAo] with a 1 h temporary occlusion of the contralateral CCA), the levels of four major membrane fatty acids (palmitic, C16:0; stearic, C18:0; Oleic, C18:1 and arachidonic, C20:4) were analyzed at 3, 36 and 72 h, and 2 and 4 wk following ischemia to determine the critical point of irreversibility of the cellular plasma membrane disorganization in primary ischemic (Area 1, parietal cortex) and peri-ischemic (Area 2, tempero-occipital cortex) areas. The cortical focal ischemia resulted in time dependent differential loss in four of these major membrane fatty acids. The quantitative differences among primary and peri-ischemic areas reflected the different degree of ischemic injury inflicted to these regions. Acute treatment with ganglioside GM1 protected the further losses of all of these fatty acids and differentially restored their levels in these various injury sites over periods of time. The changes in levels of these membrane fatty acids indicate that the primary ischemic area suffers an irreversible injury and peri-ischemic area suffers reversible injury. After acute treatment (< 2 h) with ganglioside GM1, a partial recovery was observed in primary ischemic area and complete recovery was observed in peri-ischemic areas. These studies support the hypothesis that, ischemia leads to a irreversible plasma membrane disorganization which underlies the eventual cell death, and protection and restoration of these membrane changes by drugs, such as ganglioside GM1 leads to neuroprotection against ischemic injury.

Placental transfer of (3H)-GM1 and its distribution to maternal and fetal tissues of the rat.

The demonstration that ganglioside GM1 pretreatment reduced the ethanol induced neurobehavioral effects in adult pups exposed to ethanol in utero, prompted study to examine whether GM1 crosses the placenta and penetrates fetal tissues. The present results indicate that 3H-galactose labeled GM1 not only passes the placenta but also served as a substrate for the synthesis of polysialogangliosides, and remained in various tissues up to 48 h after maternal (3H)-GM1 administration.

Comparison of bioavailability and pharmacodynamics of diltiazem from two pharmaceutical preparations.

Diltiazem, a calcium channel blocker, is used in multiple divided doses daily, due to its short elimination half-life. Hence, administration as a modified release (MR) formulation is suggested. In this double blind cross-over trial, the pharmacokinetics and pharmacodynamics of diltiazem was studied in eight healthy Indian adults. Diltiazem was administered as single dose (60 mg) of the two formulations viz immediate release (IR) and MR. Venous blood samples, for estimation of diltiazem by HPLC, were collected at frequent intervals and BP, HR and ECG were monitored during the 12h study period. With MR formulation, plasma half-life was significantly (P < 0.05) prolonged (6.25 +/- 1.2 h vs. 2.69 +/- 0.2 h), the extent of alterations in BP, HR and PR interval was significantly less, while the duration of prolongation of PR interval was significantly more as compared to IR formulation. Therefore, MR formulation of diltiazem has better pharmacokinetic and pharmacodynamic profile as compared to IR formulation.

Osteomyelitis: a rare complications of Salmonella senftenberg infection--a case report.

A case of chronic osteomyelitis is rare complication of salmonella senftenberg infection and is reported.

Altered sensitivity to acetylcholine during chronic administration of organophosphorus anticholinesterase (fenthion) in albino mice.

Tissue sensitivity to acetylcholine during chronic administration of fenthion was assessed in mice. Fenthion was injected intra-muscularly every fourth day and experiments were carried out at various intervals. The parameters selected for testing cholinergic effects were, acetyl choline-induced contraction of isolated ileum and salivary secretion in vivo. In both types of experiments an initial supersensitivity followed by tolerance to acetylcholine were observed. The underlying mechanisms are discussed.