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.

N-Acetylcysteine Amide against Aß-Induced Alzheimer's-like Pathology in Rats.

Oxidative stress with a depletion of glutathione is a key factor in the initiation and progression of Alzheimer's disease (AD). N-Acetylcysteine (NAC), a glutathione precursor, provides neuroprotective effects in AD animal models. Its amide form, N-Acetylcysteine amide (NACA), has an extended bioavailability compared to NAC. This study evaluates the neuroprotective effects of NACA against Aß1-42 peptide-induced AD-like pathology in rats. Male Wistar rats (2.5 months old) were divided into five groups: Normal Control (NC), Sham (SH), Aß, Aß + NACA and NACA + Aß + NACA (n = 8 in all groups). AD-like pathology was induced by the intracerebroventricular infusion of Aß1-42 peptide into the lateral ventricle. NACA (75 mg/kg) was administered either as a restorative (i.e., injection of NACA for 7 consecutive days after inducing AD-like pathology (Aß + N group)), or as prophylactic (for 7 days before and 7 days after inducing the pathology (N + Aß + N group)). Learning and memory, neurogenesis, expression of AD pathology markers, antioxidant parameters, neuroprotection, astrogliosis and microgliosis were studied in the hippocampus and the prefrontal cortex. All data were analyzed with a one-way ANOVA test followed by Bonferroni's multiple comparison test. NACA treatment reversed the cognitive deficits and reduced oxidative stress in the hippocampus and prefrontal cortex. Western blot analysis for Tau, Synaptophysin and Aß, as well as a histopathological evaluation through immunostaining for neurogenesis, the expression of neurofibrillary tangles, ß-amyloid peptide, synaptophysin, neuronal morphology and gliosis, showed a neuroprotective effect of NACA. In conclusion, this study demonstrates the neuroprotective effects of NACA against ß-amyloid induced AD-like pathology.

Erythematous Linear Lesion on the Course of Superficial Fibular Nerve After the Topical Application of Black Henna: A Case Report.

Henna is commonly used in body arts, where it produces orange-brown color. It is often mixed with chemicals such as para-phenylenediamine (PPD) to fasten the dyeing process and produce a black color. However, PPD has many allergic and toxic effects. We present a case of henna-induced cutaneous neuritis, which is not reported before. A 27-year-old female presented to our hospital, complaining of pain in her left great toe after applying black henna. Upon examination, the proximal nail fold was inflamed, and an erythematous non-palpable tender lesion was noticed on the dorsum of the foot. The lesion had an inverted-Y shape that was confined to the course of the superficial fibular nerve. Cutaneous nerve inflammation was favored after excluding all the anatomical structures in the region. Black henna should be avoided since it contains PPD, which can be absorbed through the skin and affect the underlying cutaneous nerves.

Using Absorbable Sutures for Traumatic Wound Closure to Avoid Additional Hospital Visits for Suture Removal During the COVID-19 Pandemic: A Randomized Controlled Trial.

Introduction The COVID-19 pandemic worldwide forced governments to undertake intervention measures to encourage social distancing. Meanwhile, traumatic skin lacerations require multiple hospital visits for dressing changing and suture removal since they are usually repaired with non-absorbable sutures. These visits can be avoided by using absorbable sutures instead. However, absorbable sutures carry the "potential" risk of wound infection. In the current study, our first objective was to determine the non-inferiority of absorbable sutures regarding infection rate after repairing traumatic wound lacerations in comparison to the conventional non-absorbable ones. Our second objective was to evaluate the superiority of absorbable sutures in regard to postoperative clinic visits for suture removal and wound dressing compared to the non-absorbable ones. Methods A sample of 471 patients with traumatic skin lacerations was analyzed during the COVID-19 pandemic in April 2020. In the control group, wounds were repaired using non-absorbable sutures, while rapid-onset absorbable sutures were used in the treatment group. By conducting a phone/video call follow-up after 21 days, several parameters regarding infection signs and clinic visits were compared between both groups. Results A significant decrease in total trauma patients (45.4%) and those who required suturing (51.2%) was observed in April 2020 compared to the same month of the previous four years (p = 0.001 (2016), p = 0.027 (2017), p = 0.027 (2018), and p = 0.001 (2019)). Regarding wound infection, no statistically significant difference (p = 0.623) was observed between the absorbable (3.2%) and non-absorbable (4.9%) groups. Using absorbable sutures resulted in significantly (p < 0.001) fewer postoperative hospital visits compared to using non-absorbable sutures (mean: one versus three visits). Conclusion Using absorbable sutures to repair traumatic wound lacerations is safe regarding wound healing and infection rates. They also reduce postoperative hospital visits since they are not intended to be removed. Therefore, they should be considered during a pandemic to reduce hospital visits for suture removal, which will subsequently enhance social distancing and relieve hospital load.

Effect of N-Acetyl Cysteine on Intracerebroventricular Colchicine Induced Cognitive Deficits, Beta Amyloid Pathology, and Glial Cells.

Among the many factors responsible for the cognitive decline in Alzheimer's disease, beta amyloid protein and plaque formation is crucial. This amyloid pathology is associated with activation of glial cells and oxidative stress but whether oxidative stress activates beta amyloid protein in the neurons is not clear. Further the expression of microglia is also known to vary during pathogenesis of beta amyloid plaques. The aim of the present study is to evaluate the antioxidant effect of NAC on amyloid pathology and cognition and also to investigate the link between amyloid pathology and glial cells activation. Intracerebroventricular colchicine in rats known mimics human AD in many aspects including memory loss, oxidative stress, and hyper phosphorylation of tau protein. The animal groups consisted of age matched control, sham operated, AD, and NAC treated in AD models of rats. Cognitive function was evaluated in active avoidance test; beta amyloid protein, beta amyloid plaques, astrocytes, and microglia cells were quantified using immunohistochemistry in hippocampal and prefrontal cortices. Colchicine has resulted in significant cognitive loss, increased intraneuronal beta amyloid protein expression, increased reactive astrocytes, and activated microglia in all the regions of the hippocampus and prefrontal cortices. The antioxidant NAC has reversed the cognitive deficits and inhibited microglia activation but failed to inhibit BAP expression and astrocytosis. Intraneuronal BAP accumulation is deleterious and known to adversely affect cognition, but in this study in spite of intraneuronal BAP accumulation, the cognition is restored. It can be postulated that NAC might have reversed the effect of intraneuronal beta amyloid protein by acting on some downstream compensatory mechanisms which needs to be explored.

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 ß-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.

Neuroprotective Role of N-acetylcysteine against Learning Deficits and Altered Brain Neurotransmitters in Rat Pups Subjected to Prenatal Stress.

Prenatal adversaries like stress are known to harm the progeny and oxidative stress, which is known to be one of the causative factors. N-acetyl cysteine (NAC), which is a potent antioxidant, has been shown to play a neuroprotective role in humans and experimental animals. This study examines the benefits of NAC on the prenatal stress-induced learning and memory deficits and alteration in brain neurotransmitter in rat pups. Pregnant dams were restrained (45 min; 3 times/day) during the early or late gestational period. Other groups received early or late gestational restrain stress combined with NAC treatment throughout the gestational period. At postnatal day (PND) 28, offspring were tested in a shuttle box for assessing learning and memory, which was followed by a brain neurotransmitter (dopamine, norepinephrine, and serotonin) estimation on PND 36. Late gestational stress resulted in learning deficits, the inability to retain the memory, and reduced brain dopamine content while not affecting norepinephrine and serotonin. NAC treatment in prenatally stressed rats reversed learning and memory deficits as well as brain dopamine content in offspring. These findings suggest that NAC protect the progeny from an undesirable cognitive sequel associated with prenatal stress.

Status of the brain antioxidant system at different growing periods after prenatal stress and N -acetyl cysteine administration.

Prenatal stress-induced neurobehavioral deficits observed in offspring are multifactorial, including oxidative stress in the developing brain. The time by which the developing brain acquires self-defense against oxidative stress is not clear. Hence in the present study we aimed to evaluate the brain antioxidant status during different developing periods. Further the study also evaluates the role of the glutathione precursor, N-acetyl cysteine (NAC) on the brain antioxidant status. Pregnant rats were subjected to restraint stress during an early or late gestational period. Another set of rats received NAC during the entire gestational period along with early or late gestational stress. The study parameters included several antioxidant studies directly from rat brain homogenate on postnatal day 24 or 48. Early or late gestational stress has caused severe oxidative stress in the developing brain on postnatal day 24 in all the parameters studied. However, brain reduced glutathione (GSH), superoxide dismutase (SOD) and total antioxidant activity (TAO) were not affected by either early or late gestational stress on postnatal day 48, but the brain malondialdehyde (MDA) level remained high and brain glutathione reductase (GSS-Rd) level remained low on postnatal day 48. Prenatal NAC treatment has reversed the oxidative damage in all the parameters on postnatal day 24 and also the brain MDA level and GSS-Rd level on postnatal day 48. This study confirms that the growing brain acquires antioxidant capacity over time but during early postnatal development it is vulnerable to oxidative stress and related neurological consequences. N-acetyl cysteine treatment during the prenatal period as an antioxidant supplement exerted a beneficiary effect in this study. Hence glutathione supplement in the nutritional source would be an idealistic approach to prenatal stress-induced neurological comorbidities in children..

Anatomical variations of the arrangement of structures at the pulmonary hilum: a cadaveric study.

PURPOSE: The aim was to study the anatomical variations of the arrangement of structures at the hilum of the lung. METHODS: The present study examined the hila of 110 cadaveric lung specimens of south Indian population. The anatomical variations of the arrangement of structures at the hilum were macroscopically observed. RESULTS: It was observed that the variations were higher in the left lung than in the right lung. The variations were observed in 16.1 % of right lungs and 48.2 % of the left lungs. There were some interesting anatomical variations like the two upper pulmonary veins, two pulmonary artery, two bronchi in the hilum of the left lung, three bronchi, four pulmonary veins and four bronchi. The present study was compared with a similar study from the same geographical location. It was observed that the frequency of variations and the hilar morphology of the arrangement of structures differ among the two separate studies from south India. CONCLUSIONS: The observations of the present study suggest that the pulmonary hilar morphology is extremely variable.

Resveratrol for prenatal-stress-induced oxidative damage in growing brain and its consequences on survival of neurons.

BACKGROUND: Prenatal-stress-induced neuronal damage in offspring is multifactorial, including oxidative damage in the developing brain. Resveratrol is known to exert its neuroprotective potentials by upregulating several antioxidant systems. Hence, the study was undertaken to evaluate the neuroprotective effect of resveratrol against prenatal-stress-induced hippocampal damage and oxidative damage in neonate rat brains. METHODS: Pregnant rats were subjected to restraint stress during early or late gestational period. Another set of rats received resveratrol during the entire gestational period along with early or late gestational stress. The study parameters included several antioxidant studies directly from rat brain homogenate on the 40th postnatal day and hippocampal neuronal assay on the 21st postnatal day. RESULTS: Early as well as late gestational stress resulted in a significant increase in lipid peroxidation and advanced oxidation protein products and decrease in total antioxidant activity and nitric oxide levels in rat brain homogenate. The neurons of the dentate gyrus were severely affected in early and late gestational stress, and only the neurons of the CA3 region were adversely affected in late gestational stress. Administration of resveratrol reversed the prenatal-stress-induced oxidative damage and neurons of dentate gyrus but not the CA3 hippocampal neurons. CONCLUSIONS: These results show the neuroprotective abilities of resveratrol against prenatal-stress-induced oxidative damage in neonatal rat brain.

Anatomical and morphometric analysis of accessory infraorbital foramen.

The aim of the present study was to analyze the anatomical and morphometric variation in shape, frequency of occurrence, direction, and position of accessory infraorbital foramen (AIOF) in relation to infraorbital foramen (IOF) in cadaveric dry skulls to minimize clinical complications and aid in surgical maneuvering in the maxillofacial region and implementing the regional block anesthesia. The IOF is an important anatomical landmark in these surgical manipulations. Because there is limited literature available on AIOF, which transmits accessory branch of the infraorbital nerve, the present study was designed. In the current study, 45 human dry skulls and 20 disarticulated maxillae have been used irrespective of sex. The other parameters included measuring the distance of AIOF from anterior nasal spine, frontomaxillary suture, infraorbital margin, IOF, and zygomaticomaxillary suture. The transverse and vertical diameter of foramen was also noted. All these measurements were taken using a digital caliper. The result of our study reveals that the presence of AIOF is more on the right side compared with the left side. Because the presence of accessory infraorbital nerve needs to be taken care of during maxillofacial surgical interventions, knowledge regarding the presence of AIOF should be taken into consideration for preoperative evaluation.

Resveratrol improves postnatal hippocampal neurogenesis and brain derived neurotrophic factor in prenatally stressed rats.

Prenatal stress induced neuronal dysfunction is multifactorial, including suppressed neurogenesis in developing brain. Resveratrol is known to exert its neuroprotective potential by enhancing neurogenesis. But the efficacy of resveratrol against prenatal stress was not addressed in detail. Hence in the present study we evaluated the neuroprotective action of resveratrol on prenatal stress-induced impaired neurogenesis. Pregnant rats were subjected to restraint stress during early or late gestational period. Another sets of rats received resveratrol during entire gestational period along with early or late gestational stress. The study parameters included neuronal assay of doublecortin positive neurons (DCX +ve) and brain derived neurotrophic factor (BDNF) estimations in 40th postnatal day rat brain. Both early and late gestational stress resulted in significant decrease in generation of new born neurons and BDNF expression in hippocampus. The decrease in number of DCX +ve neurons and hippocampal BDNF expression was more profound in the offspring who received late gestational stress compared to early gestational stress. Resveratrol treatment has improved the expression of DCX +ve neurons and BDNF expression. These data suggest the neuroprotective efficacy of resveratrol against prenatal stress induced impaired neurogenesis.

Neuroprotective effect of resveratrol against prenatal stress induced cognitive impairment and possible involvement of Na(+), K(+)-ATPase activity.

Resveratrol, an active ingredient of red wine extracts, has been shown to exhibit neuroprotective effects in several experimental models. Hence in the present study, the protective effects of resveratrol on cognitive deficits induced by prenatal stress were evaluated in offspring, and the possible involvement of Na(+), K(+)-ATPase in learning deficits were explored. Pregnant rats were subjected to restraint stress during early or late gestational period. Another set of rats received resveratrol during the entire gestational period along with early or late gestational stress. The study parameters included various behavioral tests like open field test and Morris water maze test. At the end of the behavioral tests (on 40th postnatal day), the offspring were sacrificed, and their brain homogenate was subjected to Na(+), K(+)-ATPase estimation. Early and late gestational stress affected spatial learning and memory and prenatal resveratrol has reversed these cognitive deficits. The Na(+), K(+)-ATPase activity in the offspring brain homogenate was reduced in the late gestational stress group; however prenatal resveratrol treatment has not affected this activity. These data suggest the neuroprotective efficacy of resveratrol against prenatal stress induced cognitive impairment. Though late gestational stress involves Na(+), K(+)-ATPase activity in rat brain homogenate, this would not be the primary cause in prenatal stress-induced cognitive dysfunction.

Effect of prenatal stress on expression of glutathione system in neonatal rat brain.

AIM: Prenatal stress is known to adversely affect the fetal brain development and also neuronal loss. The mechanism(s) associated with prenatal stress induced developmental neurotoxicity remains obscure. Few studies point to the glutathione (GSH) antioxidant system which is an important molecular target for this toxicant. Hence the present study investigates the effect of prenatal stress on glutathione system in neonatal rat brain. MATERIAL AND METHODS: Three to four months old pregnant Wistar rats were subjected to restraint stress during early or late gestational period. The offspring were sacrificed on 40th day and their brain homogenate was subjected to antioxidant studies. The serum corticosterone and adrenal ascorbic acid levels were also estimated from offspring. RESULTS: The prenatal stress has resulted in an increase in the serum corticosterone and reduced adrenal ascorbic acid levels in neonatal pups. Prenatal stress during early or late gestation life showed reduced glutathione, glutathione reductase (GSSG-Rd) and superoxide dismutase (SOD) activity in offspring brain homogenate. CONCLUSION: These data suggest that stress during early or late gestation period affect glutathione system in developing neonatal rat brain, which is associated with elevated serum corticosterone and reduced adrenal ascorbic acid levels.

Bilateral calcified stylohyoid ligament: an incidental autopsy finding with medicolegal significance.

Eagle's syndrome occurs due to elongation of the styloid process or calcification of the stylohyoid ligament, which then may produce a pain sensation due to pressure exerted on various structures in the head and neck region. A case report of calcified stylohyoid ligament found incidentally at autopsy and further confirmed by computed tomography scan and histopathology is herein discussed with associated medicolegal significance.

Extensor carpi radialis brevis origin, nerve supply and its role in lateral epicondylitis.

Lateral epicondylitis (LE) or tennis elbow has been the subject of concern during the last 60 years, but the pathogenesis of the LE remains unclear. The LE can be due to the tendinogenic, articular or neurogenic reasons. Numerous theories have been put fourth in the recent past, out of which one of the most popular theories is that the condition results from repeated contraction of the wrist extensor muscles, especially the extensor carpi radialis brevis (ECRB) which may compress the posterior branch of the radial nerve (PBRN) at the elbow during pronation. We studied 72 upper limbs (36 formalin-fixed cadaver) for the origin, nerve supply and the course of PBRN in relation to the ECRB as one of the goal for the present study. The possible presence of an arch of the ECRB around the PBRN was also observed and recorded. The nerve to ECRB was a branch from the radial nerve in 11 cases (15.2%); from the PBRN in 36 cases (50%) and from the superficial branch of the radial nerve in 25 cases (34.7%), respectively. The ECRB had a tendinous arch in 21 cases (29.1%); a muscular arch in 8 (11.1%) cases and the arch was absent in 43 cases (59.7%). When the ECRB had a tendinous or muscular arch around the PBRN, it may compress the same and this condition may worsen during the repeated supination and pronation as observed in tennis and cricket players. The presence of such tendinous or muscular arch should be considered by orthopedicians and neurosurgeons, while releasing the PBRN during LE surgery.

Case report of high origin of radial, ulnar, and profunda brachii arteries, its clinical implications and review of the literature / Relato de caso de origem alta das artérias radial, ulnar e braquial profunda, suas implicações clínicas e revisão de literatura

Arterial variations in the arm are of potential clinical implications as it is a frequent site of injury and also involved in many surgical and invasive procedures. During a dissection of the right upper extremity, an abnormal high origin of the radial and ulnar arteries was found. The brachial artery had a very short segment without any branches, divided into the radial and ulnar arteries at the upper third of the arm. The course and branching pattern of these radial and ulnar arteries in the arm are discussed. It was also observed that the profunda brachii artery was represented by two separate branches arising from the posterior circumflex humeral artery. Accurate knowledge of these variation patterns is of considerable clinical importance in the conduct of reparative surgeries around the shoulder and fracture management of the humerus. These additional data of arterial anomalies to contemporary anatomical literature are of interest to clinicians, in particular vascular and plastic surgeons and radiologists.

As variações arteriais no braço têm potenciais implicações clínicas já que o braço é um sítio de lesões frequentes, além de estar envolvido em muitos procedimentos cirúrgicos e invasivos. Durante a dissecção da extremidade superior direita, uma origem alta anormal das artérias radial e ulnar foi encontrada. A artéria braquial apresentava um segmento muito curto sem quaisquer ramos, dividindo-se nas artérias radial e ulnar no terço superior do braço. O curso e o padrão de ramificação das artérias radial e ulnar no braço são discutidos. Também se observou que a artéria braquial profunda estava representada por dois ramos separados, surgindo da artéria umeral circunflexa posterior. O conhecimento preciso sobre esses padrões de variação é de considerável importância na realização de cirurgias reparadoras na região do ombro e no manejo de fraturas de úmero. Estes dados adicionais sobre as anomalias arteriais para a literatura anatômica contemporânea são de grande interesse para os médicos, especialmente para cirurgiões plásticos e vasculares e radiologistas.

Dual innervations of mylohyoid muscle: a case report.

Mylohyoid and anterior belly of the digastric muscles are supplied by a branch from the inferior alveolar nerve called the mylohyoid branch. Here we present an unusual finding in a 60-year-old male cadaver in which the mylohyoid muscle is supplied by a branch from hypoglossal nerve in addition to its usual nerve supply. Hypoglossal nerve after giving superior root of the ansa cervicalis and muscular branches to thyrohyoid and geniohyoid muscles gave another branch to supply the mylohyoid muscle. Any variation in the formation and/or branching pattern of ansa cervicalis or hypoglossal nerve can cause confusion and may complicate the procedures involving this nerve such as skull base surgery, neck dissection, and anterior cervical spinal approach. Developmentally mylohyoid muscle is from the mesoderm of the first arch, therefore, must be innervated by the mandibular nerve. Hence, we report this uncommon variation based on embryology and the clinical implications.