Biomedical subjects

Shashi Wadhwa

Publications and source records attributed to Shashi Wadhwa.

16 recordsLinked to original sources

PubMed2006

The occurrence of cone inclusions in the ageing human retina and their possible effect upon vision: an electron microscope study.

During normal ageing, photoreceptors of the human retina undergo various structural changes. We examined retinas from 33 donors (56 eyes; age span 13-94 years) by electron microscopy to see morphological changes in the cones with ageing. We show mitochondrial alterations and occurrence of electron-dense globules in the cone inner segments from the fifth decade of life. The globules are more prevalent in the macular cones than those in the mid-peripheral or nasal retinas (p<0.05) and absent in peripheral retinal cones and rods. They peak in the sixth decade and then decline in the seventh decade (p<0.05), from seventh to ninth decade, however, there was no significant change in their occurrence in the cones. We also show a type of inclusion, made up of bundled microtubules, which occur exclusively in the macular cones at the eighth decade of life. Evidence suggests that altered cone mitochondria with cristae remnants and dense matrix participate in globule formation in the ageing retina. Such mitochondrial changes may cause energy depletion, and bundling of microtubules (to form filamentous inclusions) could result in decreasing intracellular transport, in which case cones may die in the long run. These factors may be responsible for reported cone loss in the human retina with ageing.

Adolescent↗

PubMed2006

Prenatal acoustic stimulation influences neuronal size and the expression of calcium-binding proteins (calbindin D-28K and parvalbumin) in chick hippocampus.

Prenatal auditory enrichment by species-specific sounds and sitar music enhances the expression of immediate early genes, synaptic proteins and calcium binding proteins (CaBPs) as well as modifies the structural components of the brainstem auditory nuclei and auditory imprinting area in chicks. There is also facilitation of postnatal auditory preference of the chicks to maternal calls following both types of sound stimulation indicating prenatal perceptual learning. To examine whether the sound enrichment protocol also affects the areas related to learning and memory, we assessed morphological changes in the hippocampus at post-hatch day 1 of control and prenatally sound-stimulated chicks. Additionally, the proportions of neurons containing calbindin D-28K and parvalbumin immunoreactivity as well as their protein levels were determined. Fertilized eggs of domestic chick were incubated under normal conditions of temperature, humidity, forced draft of air as well as light and dark (12:12h) photoperiods. They were exposed to patterned sounds of species-specific and sitar music at 65 dB for 15 min per hour over a day/night cycle from day 10 of incubation till hatching. The hippocampal volume, neuronal nuclear size and total number of neurons showed a significant increase in the music-stimulated group as compared to the species-specific sound-stimulated and control groups. However, in both the auditory-stimulated groups the protein levels of calbindin and parvalbumin as well as the percentage of the immunopositive neurons were increased. The enhanced proportion of CaBPs in the sound-enriched groups suggests greater Ca(2+) influx, which may influence long-term potentiation and short-term memory.

Acoustic Stimulation↗

PubMed2006

Vascular changes of the retina and choroid in systemic lupus erythematosus: pathology and pathogenesis.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects multiple organ systems. When eyes are involved, the principle manifestations are hemorrhage, retinal cotton wool spots, microangiopathy and vaso-occlusion. Research in the past two decades has significantly contributed to our understanding about this disease in general and its therapeutic management, although knowledge about the mechanism of ocular involvement and pathogenesis in SLE is limited. This is an important issue, because the ocular symptoms in this disease could be potentially sight threatening in acute cases. Here, we present an overview of the clinical and histopathologic features of retinal and choroidal vascular changes, as seen in patients with SLE. We discuss the role of immune complex deposition in vascular pathogenesis in the eye. Reports indicated an involvement of antiphospholipid antibodies (APAs) in the retinal and choroidal vasculopathy in SLE, although their precise role in this process is uncertain. It is important to look for mechanisms of immune complex-mediated vasculopathy and role of inflammatory mediators in this process in SLE. For this, established animal models can be utilized in research to learn about the precise role of various autoantibodies and complements involved in disease pathogenesis. A clear knowledge about the immunopathogenesis is warranted, and the rationale for the future therapy should be based on reducing vascular inflammation as well as ameliorating autoimmunity in this disease.

Autoantibodies↗

PubMed2005

Developmentally regulated expression of c-Fos and c-Jun in the brainstem auditory nuclei of Gallus domesticus is modified by prenatal auditory enrichment.

Recognition of mother's voice by human neonates and behavioral responses of birds and animals to sounds experienced prenatally emphasize the role of sensory inputs in auditory system development. Spontaneous and experience driven neural activity influence the neural circuits' refinement in developing brain. However, cellular mechanisms endowing plasticity for such structural refinement during critical developmental periods are less understood. Sensory stimulation induces fluctuating expression of transcription factors (TFs) of Fos, Jun, and Krox families in the related brain nuclei to activate genes to synthesize proteins such as those needed for cytoskeletal structures, ion channels, and regeneration. To understand the cellular mechanism of response to prenatal auditory stimulation, we studied the expression of c-Fos and c-Jun in brainstem auditory nuclei, nucleus magnocellularis, and nucleus laminaris of the domestic chick. The chick brainstems, five each of E8 (embryonic day 8), E12, E16, E20, and posthatch day 1 were processed for immunohistochemistry as well as Western blotting and quantified using image analysis systems. In controls, c-Fos and c-Jun expression in both the nuclei was developmentally up-regulated. Reduced c-Fos expression and increase in c-Jun was temporarily observed between E12-16. In the stimulated groups, c-Fos expression was elevated while c-Jun showed a reduction matched to controls. This diametrically opposing pattern of c-Fos and c-Jun expression in response to stimulation is indicative of cell survival. Thus the expression of TFs in the auditory nuclei shows a relationship beyond a simple stimulation-activity-expression. While developmental signals control the expression of TFs, extra sensory stimulation modulates their expression to possibly support neuronal survival and enhance synthesis of other proteins.

Acoustic Stimulation↗

PubMed2005

Enhanced analgesic effect of morphine-nimodipine combination after intraspinal administration as compared to systemic administration in mice.

Calcium plays an important role in the pathophysiology of pain. A number of studies have investigated the effect of L-type calcium channel blockers on the analgesic response of morphine. However, the results are conflicting. In the present study, the antinociceptive effect of morphine (2.5 microg) and nimodipine (1 microg) co-administered intraspinally in mice was observed using the tail flick test. It was compared to the analgesic effect of these drugs (morphine - 250 microg subcutaneously; nimodipine - 100 microg intraperitoneally) after systemic administration. Nimodipine is highly lipophilic and readily crosses the blood brain barrier. Addition of nimodipine to morphine potentiated the analgesic response of the latter when administered through the intraspinal route but not when administered through systemic route. It may be due to direct inhibitory effect of morphine and nimodipine on neurons of superficial laminae of the spinal cord after binding to mu -opioid receptors and L-type calcium channels respectively.

Analgesics, Opioid↗

PubMed2005

Development of the human fetal cochlear nerve: a morphometric study.

Ontogenesis of the human peripheral auditory pathway is relatively less explored. While the distal part of the auditory perception apparatus (i.e. the cochlea) received attention, studies on the neural element carrying information to the brainstem (i.e. the cochlear nerve) are scarce. In the present study, axonal differentiation, maturation and myelination of the distal end of the human cochlear nerve (CN) were assessed using light and electron microscopy. Seven human fetuses of 12, 15, 18, 20, 22, 28 and 38 weeks' gestation (WG) were analyzed. Light microscopy revealed nerve fascicles as early as 12 WG, initially arranged loosely but later compacted by 18 WG. Myelinated fibers were clearly detected at 28 WG. Ultrastructurally, at 12 WG developing Schwann cells were present between the thin unmyelinated axons. At 15 WG, the fascicular arrangement was distinct with blood vessels in the perineurium. The maximum number of axons was found at 20 WG, which subsequently reduced to reach the adult level at 22 WG. The myelinated axons in the CN were first observed on the left side at 20 WG, following which the number and proportion of myelinated axons increased until term, incorporating both small and large axons. The right CN lagged behind in maturation. Axon size also increased with age. Thus, the maturation of the human CN commences during the mid-gestation period and produces exuberant axons that are eventually pruned at a time when axons start to myelinate. During this developmental period the human CN maintains maturational asymmetry, the functional consequences of which remain to be elucidated.

Axons↗

PubMed2005

Prenatal auditory enrichment with species-specific calls and sitar music modulates expression of Bcl-2 and Bax to alter programmed cell death in developing chick auditory nuclei.

Postnatal auditory stimulation influences early perceptual learning. Previously we reported morphological effects of prenatal auditory stimulation by species-specific and sitar musical sounds on the chick brainstem auditory nuclei-nucleus magnocellularis and nucleus laminaris. At hatching, these two nuclei of auditory enriched embryos showed higher neuronal numbers, amongst other morphological changes. There were also increases in synaptophysin and syntaxin1 expressions in the sound enriched groups and modulation of the developmental expression of transcription factors c-Fos and c-Jun. We hypothesized that prenatal auditory enrichment may have reduced embryonic apoptosis in these nuclei with possible alteration of molecular mechanisms enhancing the postsynaptic neuron's ability to survive. In the present study, therefore, we examined apoptotic cell death by TUNEL technique and Bcl-2 expression using immunohistochemistry and immunoblotting. In the controls, a peak percentage in the TUNEL-positive cells was noted in the auditory nuclei at embryonic day 12, which was reduced at embryonic day 16. Bcl-2 immunoreactivity decreased from embryonic day 8 to embryonic day 12 overlapping the period of embryonic cell death in these nuclei. The stimulated groups, however, showed fewer apoptotic neurons and higher Bcl-2 level than that in the controls. On the other hand, Bax immunohistochemistry showed correlated reverse changes compared to Bcl-2 expression. Thus prenatal extra-acoustic stimulation appears to alter Bcl-2 and Bax expression to support cell survival and differentiation, thereby augmenting the development of auditory nuclei.

Acoustic Stimulation↗

PubMed2005

Expression of opioid receptor-like 1 (ORL1) & mu opioid receptors in the spinal cord of morphine tolerant mice.

BACKGROUND & OBJECTIVE: The mechanism underlying the development of tolerance to morphine is not clearly understood though a number of factors have been implicated. One of the likely factors may be increased activity of anti-opioid peptides like nociceptin (also known as orphanin FQ or N/OFQ). N/OFQ and morphine bind to opioid receptor-like 1 (ORL1) receptor and muopioid receptor respectively. The present work was undertaken to investigate the density of ORL1 and mu (mu) receptor expression in the spinal cord of mice after inducing morphine tolerance. METHODS: Swiss albino mice were injected with either morphine (experimental group, n=15) or saline (control, n=15), twice a day for 9 days. The development of tolerance was noted by the hotplate test. Cryostat sections of the cervical region of spinal cord were labeled with specific ligands to localize ORL1 and mu receptors. The density of receptor expression over laminae I-II of spinal cord was evaluated using image analysis system. RESULTS: The morphine treated mice developed tolerance by day 9 as evident by the hot plate test. Both receptors were selectively expressed at a higher concentration over the superficial laminae (I-II) of the dorsal horn, indicating a role in pain processing. An increased expression of ORL1 receptors was also noted over the gray matter around the central canal. Quantitative analysis showed an increased expression of ORL1 and mu receptors though the increase was not statistically significant. INTERPRETATION & CONCLUSION: The present study showed that both, ORL1 and mu-opioid receptors were expressed in areas of the spinal cord, concerned with transmission of pain signals. The density of these receptors increased in the superficial laminae (I-II) though not significantly from control after morphine tolerance. The increase in ORL1 receptors could oppose the analgesic action of morphine, contributing to tolerance. Further studies need to be done to elucidate the mechanism of morphine tolerance.

Animals↗

PubMed2005

Acute analgesic effect of loperamide as compared to morphine after intrathecal administration in rat.

Loperamide, a mu opioid receptor agonist, which is commonly used as an antidiarrhoeal agent has been reported to possess analgesic activity after intrathecal administration. However, the exact analgesic profile, i.e., onset, duration and intensity of analgesia in relation to morphine is not fully known. In the present study, the acute analgesic effect of loperamide (5 microg) was compared with that of morphine (5 microg) and morphine + loperamide (5 microg of each) using the tail flick method after intrathecal administration. Naloxone (5 mg/kg) reversibility of the analgesic effect was also studied. The analgesic response of loperamide was significantly higher than morphine. Even after 22 hr, maximum possible effect was greater than 49%. Naloxone partially antagonized the analgesic effect of loperamide. This suggested that loperamide may be acting through blockade of Ca2+ channels besides activating mu opioid receptors. Loperamide may prove to be a better substitute for morphine as spinal analgesic.

Analgesics↗

PubMed2004

Ontogeny of two calcium-binding proteins (calbindin D-28K and parvalbumin) in the human inferior olivary complex and their distribution in the adults.

The inferior olivary complex (IOC) is a prominent nuclear relay system of the medulla oblongata. Anatomically, it is connected to the cerebellum for coordination of motor activities. Calbindin D-28K (CALB) and parvalbumin (PV) are cytosolic calcium-binding proteins (CBP) that play a role in Ca2+ homeostasis. We examined their ontogeny and distribution in the fetal, postnatal and adult human IOC by immunohistochemistry. At 11-12 weeks of gestation (wg), calbindin immunoreactivity was present in the principal olive and the medial accessory olive, it was absent in the dorsal olive. Parvalbumin immunoreactivity developed at 16-17 wg in the ventral lamella and the lateral bulge of the principal olive only. Calbindin expression gradually increased from 20 to 37 wg, whilst by contrast, parvalbumin expression was moderate. By 37 wg, all three IOC subnuclei were immunopositive for both proteins. In a 3-month-old infant, parvalbumin was intensely developed in the olivary axons. In the adults (40- to 59-year-old), calbindin was distributed in most neurons, and olivocerebellar fibres, whereas parvalbumin was present in some neurons and few fibres. Parvalbumin expressed till 51 years, and disappeared by 59 years of age. Calbindin immunoreactivity in the olivary axons was declined at 70 years of age. The data suggest a differential distribution and requirement of these proteins in the human IOC maturation. It may be that the IOC utilizes mainly calbindin for Ca2+ buffering. The loss of parvalbumin with ageing might influence the excitability of the spared IOC neurons.

Adult↗

PubMed2004

Expression of mu-opioid receptors in developing rat spinal cord: an autoradiographic study.

The expression of mu-opioid receptors in the developing rat spinal cord (Postnatal days 7, 14, 30) was studied by autoradiography using [3H]DAMGO. When compared to camera lucida drawings, the receptor was noted over the entire gray matter and dorsal root ganglia at postnatal days 7 and 14. At postnatal day 30, the receptor expression decreased over the gray matter except the superficial laminae (laminae I and II). At all age groups studied, a higher expression of the receptor was noted over the superficial laminae. The study shows that micro-opioid receptors appears early in postnatal development and attains mature receptor distribution relatively late in ontogeny, suggesting a possible role in the normal development of nervous system. This is affirmed by an impairment of psychomotor development in babies born to mothers, addicted to opiates.

Animals↗

PubMed2004

Effect of prenatal species-specific and music stimulation on the postnatal auditory preference of domestic chick.

Perinatal sensory experience plays an important role in the development of perceptual preferences. In the present study prenatal enrichment with sound stimulus was given to see its effect on the development of postnatal auditory preference. Auditory stimulation with either species-specific (chicken maternal and hatching calls) or music (slow and fast sitar music) sounds was provided to two separate sets of fertilized eggs from the day 10 of incubation. The postnatal auditory preference of the chicks to either species-specific or music sounds was then tested at different time periods after hatching. All the chicks, irrespective of the type of prenatal exposure, showed preference for species-specific maternal calls. Notably, the music stimulated chicks did not show preference for either slow or fast music. In both the experimental groups, the number of chicks responding to the species-specific maternal calls was significantly (P<0.001) more at 24 h and 48 h post hatch, when compared with the unstimulated control group. Comparison of the species-specific stimulated group with the music stimulated group, for auditory preference to the maternal calls, did not show any significant difference. Further, in the species-specific sound stimulated groups, there was a significant (P<0.001) increase in the number of chicks responding to maternal calls at 60 h of age with repeated testing. However, there was no effect of peer imprinting on the auditory preference of the chicks, in both the experimental groups. The results indicate that prenatal auditory experience with either species-specific or non-specific music enhances the postnatal auditory preference of chicks for the species-specific sounds.

Acoustic Stimulation↗

PubMed2003

Expression of the neurotrophin receptors Trk A and Trk B in adult human astrocytoma and glioblastoma.

Neurotrophins and their receptors of the Trk family play a critical role in proliferation, differentiation and survival of the developing neurons. There are reports on their expression in neoplasms too, namely, the primitive neuroectodermal tumours of childhood, and in adult astrocytic gliomas. The involvement of Trk receptors in tumour pathogenesis, if any, is not known. With this end in view, the present study has examined 10 tumour biopsy samples (identified as astrocytoma, pilocytic astrocytoma and glioblastoma) and peritumoral brain tissue of adult patients, for the presence of Trk A and Trk B receptors, by immunohistochemistry. The nature of the tumour samples was also confirmed by their immunoreactivity (IR) to glial fibrillary acidic protein. In the peritumoral brain tissue, only neurons showed IR for Trk A and Trk B. On the contrary, in the tumour sections, the IR to both receptors was localized in the vast majority of glia and capillary endothelium. There was an obvious pattern of IR in these gliomas: high levels of IR were present in the low-grade (type I and II) astrocytoma; whereas in the advanced malignant forms (WHO grade IV giant cell glioblastoma and glioblastoma multiforme) the IR was very weak. These findings suggest that Trk A and Trk B are involved in tumour pathogenesis, especially in the early stage, and may respond to signals that elicit glial proliferation, and thus contribute to progression towards malignancy.

Adolescent↗

PubMed2003

[Transient compensatory hypertrophy and limited regeneration of the surgically removed rat ventral prostate].

OBJECTIVES: To confirm whether regeneration of prostate lobe indeed takes place on surgical lobectomy and if so, to what extent. Other issues studied are 1. whether the lobe regenerated is similar morphologically to that developing normally from neonatal origin to adulthood, and 2. the consequences of partial lobectomy on the contralateral lobe and the influence of sex steroid hormones on the regeneration process. METHODS: The effect of surgical removal of one of the ventral prostate lobes on the size of the contralateral lobe has been studied at various time intervals after lobectomy. RESULTS: The surgically extirpated ventral prostate lobe in rats regenerates attaining plateau size at 8-16 weeks post lobectomy. The regenerated lobe, however, remains significantly smaller than the original size. In early phase of post lobectomy (at 2 weeks) the contralateral lobe was significantly hypertrophied. It reverts to normal size on regeneration of the extirpated lobe with time. Orchiectomy carried out at the time of lobectomy caused a drastic reduction in the size of the remaining lobe, which was prevented by exogenous treatment with androgens. In animals receiving treatment with estrogens, the remaining lobe was partially but not fully atrophied. However, estrogens did not support the regeneration of the surgically removed lobe, which requires androgens. CONCLUSIONS: These studies demonstrate that surgical removal of one of the ventral prostate lobe leads to a process of regeneration. However, the regenerated lobe does not attain the normal size.

Animals↗

PubMed2002

Effect of prenatal sound stimulation on medio-rostral neostriatum/hyperstriatum ventrale region of chick forebrain: a morphometric and immunohistochemical study.

The higher auditory association area in chick forebrain, i.e. medio-rostral neostriatum/hyperstriatum ventrale region (MNH), is involved in juvenile auditory filial imprinting. Studies show that neuronal size as well as expression of calcium-binding proteins, parvalbumin (PV) and calbindin D28K (CaBP) are regulated by neuronal activation. In the present study, we have determined the effect of extra auditory stimulation, given as a prenatal sound enrichment protocol, on MNH neurons of posthatch day 1 chicks. Patterned species-specific or musical (sitar) sounds were provided in a graded manner from embryonic day 10 through hatching. Thionin and immunohistochemically stained (PV and CaBP) neurons were evaluated by morphometric methods. The thionin-stained MNH neurons of both the auditory stimulated groups showed a significant increase in nuclear area compared to controls. The change in nuclear dimension was greater in the music-stimulated than in the species-specific sounds-stimulated group. These observations indicate a positive influence of prenatal sound stimulation on MNH neurons. The auditory stimulated groups also demonstrated an increase in the proportion of PV- and CaBP-neurons compared to controls, with the species-specific sounds-stimulated group showing a significantly higher percentage of immunostained cells than the music-stimulated group. However, immunostained cells of both the auditory stimulated groups did not show a significant change in size. These cytoplasmic proteins, by acting as intracellular buffers, enable neurons to display high electrical activity without calcium overload. The influx of Ca(2+) ions is essential for long-term potentiation, a phenomenon important for learning and memory. The increase in percentage of the neurons containing calcium-binding proteins may provide a morphological basis for enhancement of auditory imprinting and learning.

Acoustic Stimulation↗

PubMedDate not supplied

Training of postgraduates in anatomy.

It is recognized that training methods differ among the various medical colleges; however, trained specialists should be competent to discharge their duties independently in any part of the country. Therefore, to maintain uniform standards of education, there is a need to harmonize postgraduate training in anatomy. It is proposed that a structured training programme should be drawn up and monitored regularly at specified intervals, spelling out some clearly defined targets that need to be achieved. The ultimate goal of the postgraduate training programme should be to produce anatomists with sufficient knowledge and practical skills to undertake undergraduate teaching and evaluation in all branches of anatomy, as well as to pursue research independently.

Anatomy↗