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Biomedical subjects

U Anand

Publications and source records attributed to U Anand.

11 recordsLinked to original sources

Influence of human skin injury on regeneration of sensory neurons.

The regeneration of sensory nerve fibres is regulated by trophic factors released from their target tissue, particularly the basal epidermis, and matrix molecules. Means to modulate this response may be useful for the treatment of neuromas and painful hypertrophic scars and of sensory deficits in skin grafts and flaps. We have developed an in vitro model of sensory neuron regeneration on human skin in order to study the mechanisms of sensory dysfunction in pathological conditions. Adult rat sensory neurons were co-cultured with unfixed cryosections of normal or injured (crushed) human skin for 72 h. Neurons were immunostained for growth-associated protein-43 and the neurite lengths of neuronal cell bodies situated in various skin regions were measured. Two-way analysis of variance was performed. Neurites of sensory cell bodies on epidermis of normal skin were the shortest, with a mean +/- SEM of 75+/-10 micrometer, whereas those of cells on the dermo-epidermal junction were the longest, with a mean +/- SEM of 231+/-18 micrometer. Neurons on the dermo-epidermal junction of injured skin had significantly longer neurites than those on the same region of normal skin (mean +/- SEM = 289+/-21 micrometer). Regeneration of sensory neurons may be influenced by extracellular matrix molecules, matrix-binding growth factors and trophic factors. Altered substrate or trophic factors in injured skin may explain the increase of neurite lengths. This in vitro model may be useful for studying the molecular mechanisms of sensory recovery and the development of neuropathic pain following peripheral nerve injury.

Animals↗

Calcium-activated potassium channel SK1- and IK1-like immunoreactivity in injured human sensory neurones and its regulation by neurotrophic factors.

Calcium-activated potassium ion channels SK and IK (small and intermediate conductance, respectively) may be important in the pathophysiology of pain following nerve injury, as SK channels are known to impose a period of reduced excitability after each action potential by afterhyperpolarization. We studied the presence and changes of human SK1 (hSK1)- and hIK1-like immunoreactivity in control and injured human dorsal root ganglia (DRG) and peripheral nerves and their regulation by key neurotrophic factors in cultured rat sensory neurones. Using specific antibodies, hSK-1 and hIK-1-like immunoreactivity was detected in a majority of large and small/medium-sized cell bodies of human DRG. hSK1 immunoreactivity was decreased significantly in cell bodies of avulsed human DRG (n = 8, surgery delay 8 h to 12 months). There was a decrease in hIK1-like immunoreactivity predominantly in large cells acutely (<3 weeks after injury), but also in small/medium cells of chronic cases. Twenty-three injured peripheral nerves were studied (surgery delay 8 h to 12 months); in five of these, hIK1-like immunoreactivity was detected proximally but not distally to injury, whereas neurofilament staining confirmed the presence of nerve fibres in both regions. These five nerves, unlike the others, had all undergone Wallerian degeneration previously and the loss of hIK1-like immunoreactivity may therefore reflect reduced axonal transport of this ion channel across the injury site in regenerated fibres, as well as decreased expression in the cell body. In vitro studies of neonatal rat DRG neurones showed that nerve growth factor (NGF) significantly increased the percentage of hSK1-positive cells, whereas neurotrophin 3 (NT-3) and glial cell line-derived neurotrophic factor (GDNF) failed to show a significant effect. NT-3 stimulated hIK1 expression, while NGF and GDNF were ineffective. As expected, NGF increased expression of the voltage-gated sodium channel SNS1/PN3 in this system. Decreased retrograde transport of these neurotrophic factors in injured sensory neurones may thus reduce expression of these ion channels and increase excitability. Blockade of IK1-like and other potassium channels by aminopyridines (4-AP and 3,4-DAP) may also explain the paraesthesiae induced by these medications. Selective potassium channel openers are likely to represent novel therapies for pain following nerve injury.

Adult↗

Intradialytic dobutamine therapy in maintenance hemodialysis patients with persistent hypotension.

Intradialysis hypotension is a common problem, especially in patients with poor left-ventricular function. We studied 6 patients who were on maintenance hemodialysis with left-ventricular ejection fraction of <40%, whose dialysis sessions were often complicated with severe hypotension (systolic blood pressure <90 mm Hg). Dobutamine infusion during dialysis significantly reduced the number of hypotensive episodes, increased left-ventricular ejection fraction, and decreased the number of emergency admissions to the hospital.

Adrenergic beta-Agonists↗

Vaccine-induced necrobiotic granuloma.

We report two cases of necrobiotic palisaded granulomas which developed at the site of intradermal hepatitis B vaccination. To the best of our knowledge, this kind of reaction has not been reported previously.

Adolescent↗

Preferential growth of neonatal rat dorsal root ganglion cells on homotypic peripheral nerve substrates in vitro.

Developing sensory neurons interact with molecular signals in the local environment to generate stereotypic nerve pathways. Regenerating neurons seem to lose the ability to reinnervate their original sites in the targets, resulting in abnormal sensory input and consequent clinical pathophysiology. The specificity of reinnervation of peripheral targets by regenerating axons is thus crucial for normal recovery of function. In this study, we have examined evidence for selectivity of interactions between primary afferent neurons from identified levels of the spinal cord and different peripheral nerve environments by culturing these neurons on sections of nerves to muscle and viscera. We have compared the growth of a population of sensory afferents normally innervating somatic targets (dorsal root ganglion cells from L4 and L5) with populations containing many afferents innervating visceral targets (L6 and S1 dorsal root ganglia and nodose ganglion). These neurons, from newly born rats, were cultured on unfixed cryostat sections of normal and prelesioned gastrocnemius nerve, pelvic spinal nerve and vagus nerve from adult rats. Normal muscle nerve was seen to support the regeneration of a significantly greater proportion of somatic neurons, with longer neurites, than the visceral nerves. Similarly, much higher proportions of the 'visceral' population of afferent neurons were seen to extend neurites on the normal visceral nerve substrates, with longer neurites, than on the muscle nerve substrate. The selectivity displayed by the sensory neurons for their normal nerve substrates was abolished when they were cultured on prelesioned nerve substrates subjected to Wallerian degeneration, which was apparent from the equivalent and increased proportions of growing neurons having comparable neurite lengths, on all the nerve substrates. We conclude that sensory neurons recognize and respond to substrate-specific and substrate-bound molecules present in normal adult peripheral nerves, and that these differences are lost in prelesioned nerves following Wallerian degeneration.

Animals↗

Alprazolam-induced hypomania.

OBJECTIVE: There are reports of alprazolam-induced hypomania/mania. Here is a case report of a patient who developed hypomania during treatment with alprazolam, but not with diazepam, another benzodiazepine derivative. CLINICAL PICTURE: The illness was of 2 months' duration and the patient received a diagnosis of anxious depression. Following treatment with alprazolam, the patient developed hypomania characterised by euphoria, overactivity, overtalkactivity, racing thoughts, oversocialisation, enhanced self-confidence and disturbed sleep. TREATMENT: Hypomania subsided when alprazolam was withdrawn. There was no recurrence with fluoxetine or diazepam that ameliorated the primary condition. OUTCOME: The patient was symptom-free on follow-up. CONCLUSIONS: Alprazolam can induce hypomania/mania and, perhaps, it differs from other benzodiazepines in its mode of action. Clinicians have to be alert to the possibility of their patients developing hypomania/mania while on alprazolam.

Adult↗

Anti-oxidant enzymes, gamma-glutamyl transpeptidase and lipid peroxidation in kidney of rats exposed to cigarette smoke.

Glutathione reductase (GR), glutathione peroxidase (GSH Px) and catalase (Cat) were determined in the kidneys of rats exposed to cigarette smoke for 3 months. Activity of the brush-border enzyme gamma-glutamyl transpeptidase (GGT), glutathione (GSH) and lipid peroxide levels (LPX) were also estimated in both, kidney homogenates and urine. Activities of GR, Cat, GGT and the levels of GSH were decreased in the kidney. However, the activities of GSH Px and LPX levels were increased. Urinary excretion of GGT, GSH and LPX were also higher. Fall in the activity of GR and rise in the activity of GSH Px, may perturb the reduced glutathione/oxidised glutathione ratio, which in turn could lead to increased LPX seen in chronic cigarette smoke exposure.

Animals↗

Retrograde labelling of dorsal root ganglion cells in the rat: a quantitative and morphological comparison of Fluoro-Gold with horseradish peroxidase labelling.

We have compared retrograde labelling of rat primary sensory neurons using Fluoro-Gold (FG) and horseradish peroxide conjugated with wheat germ agglutinin (HRP-WGA). Fluoro-Gold 2.5% after 48 h transit time and FG 5% after 24 and 48 h retrogradely labelled similar numbers of cell profiles as HRP-WGA (P greater than 0.1% Student's t-test). The calculated cell size distribution for the above FG groups were similar to those for the HRP-WGA. However, FG 2.5% after a 24 h transit time labelled significantly fewer cells (P less than 0.001 Student's t-test). FG retrograde transport may be used to identify the same population of DRG cells as HRP-WGA.

Animals↗

Acute effects of ethanol on production & disposal of adenosine from rat myocardium.

Adenosine is a local hormone and is considered to act as a vasodilatory substance when released locally. Alcohol is known to affect membrane structure and acts as a coronary vasodilator. Membrane enzymes such as 5'-nucleotidase, adenosine deaminase, and gammaglutamyl transpeptidase, along with AMP deaminase, have been studied in rat myocardial tissue following the administration of a sufficiently toxic dose (producing semiconsciousness) of ethanol (1ml of 7M ethanol/100g body wt.). The activity of 5'-nucleotidase as well as that of adenosine deaminase increased due to the administration of ethanol, without any significant change in the activities of gammaglutamyl transpeptidase and AMP deaminase. These changes are discussed in relation to the metabolic changes occurring in the myocardium and the resultant effects on the coronary vessels.

5'-Nucleotidase↗