N-ACETYLCYSTEINE REVERSES LATE GESTATIONAL STRESS INDUCED MATERNAL OXIDATIVE DAMAGE

Objective: This study was intended to investigate the effect of early and late gestational stress, on the levels of antioxidants and antioxidant enzymes in maternal serum that reflects oxidative damage. We also aimed at evaluating the protective role of N-acetylcysteine (NAC) against this oxidative stress. This study was carried out with speculation in mind that maternal oxidative damage could be the cause for developmental defects in off spring.Methods: Pregnant rats were exposed to restrain stress thrice daily, either during the first half or during the second half of gestation. Other groups were treated with N-acetylcysteine throughout pregnancy, along with exposure to either early gestational stress or late gestational stress. Control group was kept undisturbed throughout pregnancy. Immediately after delivery, blood was drawn to estimate the serum antioxidant levels.Results: Pregnant rats exposed to stress during the late gestational period showed significant variation in the level of serum MDA, Glutathione Reductase, reduced glutathione, SOD and total antioxidant capacity although, administration of NAC brought about improvement in the antioxidant status.Conclusion: NAC is an effective antioxidant that can bring down the oxidative damage caused by late gestational stress in rats.Â

A Comparison of Vitamin A and Leucovorin for the Prevention of Methotrexate-Induced Micronuclei Production in Rat Bone Marrow

INTRODUCTION: Methotrexate, a folate antagonist, is a mainstay treatment for childhood acute lymphoblastic leukemia. It is also widely used in a low dose formulation to treat patients with rheumatoid arthritis. In rats, methotrexate is known to induce micronuclei formation, leading to genetic damage, while vitamin A is known to protect against such methotrexate-induced genetic damage. Leucovorin (folinic acid) is generally administered with methotrexate to decrease methotrexate-induced toxicity. OBJECTIVES: We aimed to determine whether vitamin A and leucovorin differed in their capacity to prevent formation of methotrexate-induced micronuclei in rat bone marrow erythrocytes. The present study also aimed to evaluate the effect of combined treatment with vitamin A and leucovorin on the formation of methotrexate-induced micronuclei. METHODS: Male and female Wistar rats (n=8) were injected with 20 mg/kg methotrexate (single i.p. dose). The control group received an equal volume of distilled water. The third and fourth groups of rats received vitamin A (5000 IU daily dose for 4 successive days) and leucovorin (0.5 mg/kg i.p. dose for 4 successive days), respectively. The fifth and sixth groups of rats received a combination of vitamin A and a single dose of methotrexate and a combination of leucovorin and methotrexate, respectively. The last group of rats received a combination of leucovorin, vitamin A and single dose of methotrexate. Samples were collected at 24 hours after the last dose of the treatment into 5% bovine albumin. Smears were obtained and stained with May-Grunwald and Giemsa. One thousand polychromatic erythrocytes were counted per animal for the presence of micronuclei and the percentage of polychromatic erythrocyte was determined. RESULTS: Comparison of methotrexate-treated rats with the control group showed a significant increase in the percentage of cells with micronuclei and a significant decrease polychromatic erythrocyte percentage. Combined methotrexate and vitamin A therapy and combined methotrexate and leucovorin therapy led to significant decreases in the micronuclei percentage and an increase in polychromatic erythrocyte percentage when compared to rats treated with methotrexate alone. Leucovorin was found to be more effective than vitamin A against the formation of methotrexate-induced micronuclei. CONCLUSIONS: Both vitamin A and leucovorin provided significant protection against genetic damage induced by methotrexate

DOES METHYLPHENIDATE ENHANCE COGNITION IN NORMAL RATS AND DOES IT AFFECT NEURONAL POPULATION?

Objective: Methylphenidate [MPH] is one of the drugs of choice for children with Attention Deficit Hyperactivity Disorder [ADHD] since many decades with good effect. Consumption of this drug by normal children and adolescents to boost their cognition skills is of concern. MPH induced cognitive enhancement involves brain dopamine and norepinephrine levels in areas concerned with cognition especially hippocampus. Altered expression of these neurotransmitters can affect neuronal population of hippocampus which may have the significant effect in later part of the life. Hence we evaluate the effect of MPH on cognition and histopathological changes in the hippocampus and dentate gyrus.Methods: Two month old male wistar rats were given either 2 or 5 mg/kg dose of MPH for 10 successive days and another set of rats served as control. The rats were tested for learning and memory activities followed by histopathological studies in hippocampus and dentate gyrus using Nissl staining.Results: MPH at both the doses has enhanced learning abilities as well as retention of memory. The histopathological studies did not show any significant effect on dentate gyrus as well as hippocampus.Conclusion: Though MPH is known to provide sound results in ADHD, from the present study it is clear that MPH treatment in normal rats also temporarily enhance the cognitive skills especially declarative memory. However, its effect on long term memory is to be investigated. MPH treatment has not affected the neuronal population hence possible cytotoxic effects on neurons can be ruled out from the present study.Â

Anatomical Variation of Radial Wrist Extensor Muscles: A Study in Cadavers

OBJECTIVE: The tendons of the extensor carpi radialis longus and brevis muscles are quite useful in tendon transfer, such as in correction of finger clawing and restoration of thumb opposition. Knowledge of additional radial wrist extensor muscle bellies with independent tendons is useful in the above-mentioned surgical procedures. METHODS: The skin, subcutaneous tissue, and antebrachial fascia of 48 (24 on the right side and 24 on left side) male upper limb forearms were dissected. The following aspects were then analyzed: (a) the presence of additional muscle bellies of radial wrist extensors, (b) the origin and insertion of the additional muscle, and (c) measurements of the muscle bellies and their tendons. RESULTS: Five out of 48 upper limbs (10.41%) had additional radial wrist extensors; this occurred in 3 out of 24 left upper limbs (12.5%) and 2 out of 24 right upper limbs (8.3%). In one of the right upper limbs, two additional muscles were found. The length and width of each additional muscle belly and its tendon ranged between 2 - 15cm by 0.35 - 6.4cm and 2.8 - 20.8cm by 0.2 0.5cm, respectively. The additional radial wrist extensor tendons in our study basically originated either from the extensor carpi radialis longus or brevis muscles and were inserted at the base of the 2nd or 3rd metacarpal bone. CONCLUSION: The present study will inform surgeons about the different varieties of additional radial wrist extensors and the frequency of their occurrence

Prenatal Isotretinoin Exposure Reduces the Neuronal Population of Hippocampus in Rats

ABSTRACT Isotretinoin is a drug used in the treatment of acne. Teratogenic effects of isotretinoin are well known. It is causes craniofacial abnormalities like cleft palate in animal model studies. There are very few studies focusing on its effect on the developing brain specially hippocampus concerned with memory. In the present study we investigate teratogenic effect on neuronal population of the hippocampus during postnatal development. Pregnant Wistar rats were exposed to either 8 or 16mg/kg dose of body weight of isotretinoin during early or mid-gestation of pregnancy. Pups were sacrificed at postnatal day 7 or day 21, brains were removed and processed for histological studies. Coronal sections o brain were taken and stained with cresyl violet and viable neurons were counted for 250 μm length in different regions of the hippocampus. At postnatal day 7neurons belonging to CA1 region of the hippocampus was severely affected at both the doses tested and also in early & mid-gestation treatment regime. At postnatal day 21, neurons of the CA2 & CA1 regions were severely affected. It is also observed that mid-gestational effect had more severe effect compared to early gestational treatment. This study clearly demonstrates the teratogenic effect of isotretinoin on hippocampal neuronal population of developing brain. Care must be taken while prescribing this drug to women of reproductive age

Multiple variations of renal vessels and ureter

It is not very uncommon to find accessory renal artery (or arteries) or double ureter and a number of such cases have been reported. The various types of accessory renal arteries, their positions, method of entry to the kidney and its segmentation were studied extensively by David Sykes. [1] However, multiple variations in a single subject was not reported so far, with best of our knowledge. During routine dissection it was observed in one of the male cadavers that the kidney presented a number of vari-ations bilaterally. It was found that the right kidney had four (accessory) renal arteries and three renal veins. The hilum extending on to the anterior surface and presented double ureter

N-Acetyl Cysteine Supplement Minimize Tau Expression and Neuronal Loss in Animal Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by the accumulation of neurofibrillary tangles (NFT), deposition of beta amyloid plaques, and consequent neuronal loss in the brain tissue. Oxidative stress to the neurons is often attributed to AD, but its link to NFT and β-amyloid protein (BAP) still remains unclear. In an animal model of AD, we boosted the oxidative defense by N-Acetyl cysteine (NAC), a precursor of glutathione, a powerful antioxidant and free radical scavenger, to understand the link between oxidative stress and NFT. In mimicking AD, intracerebroventricular (ICV) colchicine, a microtubule disrupting agent also known to cause oxidative stress was administered to the rats. The animal groups consisted of an age-matched control, sham operated, AD, and NAC treated in AD models of rats. Cognitive function was evaluated in a passive avoidance test; neuronal degeneration was quantified using Nissl staining. NFT in the form of abnormal tau expression in different regions of the brain were evaluated through immunohistochemistry using rabbit anti-tau antibody. ICV has resulted in significant cognitive and neuronal loss in medial prefrontal cortex (MFC) and all the regions of the hippocampus. It has also resulted in increased accumulation of intraneuronal tau in the hippocampus and MFC. NAC treatment in AD model rats has reversed the cognitive loss and neuronal degeneration. The intraneuronal tau expression also minimized with NAC treatment in AD model rats. Thus, our findings suggest that an antioxidant supplement during the progression of AD is likely to prevent neuronal degeneration by minimizing the neurofibrillary degeneration in the form of tau accumulation

Serotonergic and Adrenergic Neuroreceptor Manipulation Ameliorates Core Symptoms of ADHD through Modulating Dopaminergic Receptors in Spontaneously Hypertensive Rats

The core symptoms of attention deficit hyperactivity disorder (ADHD) are due to the hypofunction of the brain’s adrenergic (NE) and dopamine (DA) systems. Drugs that enhance DA and NE neurotransmission in the brain by blocking their transporters or receptors are the current therapeutic strategies. Of late, the emerging results point out the serotonergic (5-HT) system, which indirectly modulates the DA activity in reducing the core symptoms of ADHD. On this basis, second-generation antipsychotics, which utilize 5-HT receptors, were prescribed to children with ADHD. However, it is not clear how serotonergic receptors modulate the DA activity to minimize the symptoms of ADHD. The present study investigates the efficacy of serotonergic and alpha-2 adrenergic receptor manipulation in tackling the core symptoms of ADHD and how it affects the DA neuroreceptors in the brain regions involved in ADHD. Fifteen-day-old male spontaneously hypertensive rats (SHRs) received 5-HT1A agonist (ipsapirone) or 5-HT2A antagonist (MDL 100907) (i.p.) or alpha-2 agonist (GFC) from postnatal days 15 to 42 along with age-matched Wistar Kyoto rats (WKY) (n = 8 in each group). ADHD-like behaviors were assessed using a battery of behavioral tests during postnatal days 44 to 65. After the behavioral tests, rat brains were processed to estimate the density of 5-HT1A, 5-HT2A, DA-D1, and DA-D2 neuroreceptors in the prefrontal cortex, the striatum, and the substantia nigra. All three neuroreceptor manipulations were able to minimize the core symptoms of ADHD in SHRs. The positive effect was mainly associated with the upregulation of 5-HT2A receptors in all three areas investigated, while 5-HT1A was in the prefrontal cortex and the substantia nigra. Further, the DA-D1 receptor expression was downregulated by all three neuroreceptor manipulations except for alpha-2 adrenergic receptor agonists in the striatum and 5-HT2A antagonists in the substantia nigra. The DA-D2 expression was upregulated in the striatum while downregulated in the prefrontal cortex and the substantia nigra. In this animal model study, the 5-HT1A agonist or 5-HT2A antagonist monotherapies were able to curtail the ADHD symptoms by differential expression of DA receptors in different regions of the brain