Aluminum as a Possible Cause Toward Dyslipidemia.

Aluminum, the third most abundant metal present in the earth's crust, is present almost in all daily commodities we use, and exposure to it is unavoidable. The interference of aluminum with various biochemical reactions in the body leads to detrimental health effects, out of which aluminum-induced neurodegeneration is widely studied. However, the effect of aluminum in causing dyslipidemia cannot be neglected. Dyslipidemia is a global health problem, which commences to the cosmic of non-communicable diseases. The interference of aluminum with various iron-dependent enzymatic activities in the tri-carboxylic acid cycle and electron transport chain results in decreased production of mitochondrial adenosine tri-phosphate. This ultimately contributes to oxidative stress and iron-mediated lipid peroxidation. This mitochondrial dysfunction along with modulation of α-ketoglutarate and L-carnitine perturbs lipid metabolism, leading to the atypical accumulation of lipids and dyslipidemia. Respiratory chain disruption because of the accumulation of reduced nicotinamide adenine di-nucleotide as a consequence of oxidative stress and the stimulatory effect of aluminum exposure on glycolysis causes many health issues including fat accumulation, obesity, and other hepatic disorders. One major factor contributing to dyslipidemia and enhanced pro-inflammatory responses is estrogen. Aluminum, being a metalloestrogen, modulates estrogen receptors, and in this world of industrialization and urbanization, we could corner down to metals, particularly aluminum, in the development of dyslipidemia. As per PRISMA guidelines, we did a literature search in four medical databases to give a holistic view of the possible link between aluminum exposure and various biochemical events leading to dyslipidemia.

Chronic musculoskeletal pain among elderly individuals in a rural area of West Bengal: A mixed-method study.

Introduction: The high prevalence among elderly individuals and potential adverse impact on their overall life quality make chronic musculoskeletal pain a significant public health concern. Chronic musculoskeletal pain is an important cause of self-medication, which must be addressed to avoid various side effects and improve elderly health. This study aimed to determine the prevalence of chronic musculoskeletal pain and its associated factors among individuals (age ≥60 years) in rural West Bengal and explore their perspectives and perceived barriers regarding pain and its management. Method: This mixed-method study was conducted in rural West Bengal from December 2021 to June 2022. The quantitative strand was conducted by interviewing 255 elderly participants (age ≥60 years) using a structured questionnaire. The qualitative strand was conducted via in-depth interviews of 10 patients with chronic pain. Quantitative data were analyzed using SPSS version 16, and chronic pain-related factors were analyzed using logistic regression models. Qualitative data were analyzed thematically. Results: Among the participants, 56.8% reported chronic musculoskeletal pain. The most frequently affected site was the knee joint. Comorbidity (adjusted odds ratio [aOR]=7.47, 95% confidence interval [CI]=3.2-17.5), age (aOR=5.16, 95% CI=2.2-13.5), depression (aOR=2.96, 95% CI=1.2-6.7) and over-the-counter drug usage (aOR=2.51, 95% CI=1.1-6.4) were significantly associated with chronic pain. Analgesic dependency, lack of motivation to adopt lifestyle modifications, lack of knowledge on analgesic side effects were considered pain management barriers. Conclusion: Managing comorbidities, providing mental support, generating awareness of analgesic side effects, strengthening healthcare facilities should be prioritized for holistic chronic musculoskeletal pain management.

Ocular manifestations of central insulin resistance.

Central insulin resistance, the diminished cellular sensitivity to insulin in the brain, has been implicated in diabetes mellitus, Alzheimer's disease and other neurological disorders. However, whether and how central insulin resistance plays a role in the eye remains unclear. Here, we performed intracerebroventricular injection of S961, a potent and specific blocker of insulin receptor in adult Wistar rats to test if central insulin resistance leads to pathological changes in ocular structures. 80 mg of S961 was stereotaxically injected into the lateral ventricle of the experimental group twice at 7 days apart, whereas buffer solution was injected to the sham control group. Blood samples, intraocular pressure, trabecular meshwork morphology, ciliary body markers, retinal and optic nerve integrity, and whole genome expression patterns were then evaluated. While neither blood glucose nor serum insulin level was significantly altered in the experimental or control group, we found that injection of S961 but not buffer solution significantly increased intraocular pressure at 14 and 24 days after first injection, along with reduced porosity and aquaporin 4 expression in the trabecular meshwork, and increased tumor necrosis factor α and aquaporin 4 expression in the ciliary body. In the retina, cell density and insulin receptor expression decreased in the retinal ganglion cell layer upon S961 injection. Fundus photography revealed peripapillary atrophy with vascular dysregulation in the experimental group. These retinal changes were accompanied by upregulation of pro-inflammatory and pro-apoptotic genes, downregulation of anti-inflammatory, anti-apoptotic, and neurotrophic genes, as well as dysregulation of genes involved in insulin signaling. Optic nerve histology indicated microglial activation and changes in the expression of glial fibrillary acidic protein, tumor necrosis factor α, and aquaporin 4. Molecular pathway architecture of the retina revealed the three most significant pathways involved being inflammation/cell stress, insulin signaling, and extracellular matrix regulation relevant to neurodegeneration. There was also a multimodal crosstalk between insulin signaling derangement and inflammation-related genes. Taken together, our results indicate that blocking insulin receptor signaling in the central nervous system can lead to trabecular meshwork and ciliary body dysfunction, intraocular pressure elevation, as well as inflammation, glial activation, and apoptosis in the retina and optic nerve. Given that central insulin resistance may lead to neurodegenerative phenotype in the visual system, targeting insulin signaling may hold promise for vision disorders involving the retina and optic nerve.

Acute sleep deprivation induces synaptic remodeling at the soleus muscle neuromuscular junction in rats.

Sleep is important for cognitive and physical performance. Sleep deprivation not only affects neural functions but also results in muscular fatigue. A good night's sleep reverses these functional derangements caused by sleep deprivation. The role of sleep in brain function has been extensively studied. However, its role in neuromuscular junction (NMJ) or skeletal muscle morphology is sparsely addressed although skeletal muscle atonia and suspended thermoregulation during rapid eye movement sleep possibly provide a conducive environment for the muscle to rest and repair; somewhat similar to slow-wave sleep for synaptic downscaling. In the present study, we have investigated the effect of 24 h sleep deprivation on the NMJ morphology and neurochemistry using electron microscopy and immunohistochemistry in the rat soleus muscle. Acute sleep deprivation altered synaptic ultra-structure viz. mitochondria, synaptic vesicle, synaptic proteins, basal lamina, and junctional folds needed for neuromuscular transmission. Further acute sleep deprivation showed the depletion of the neurotransmitter acetylcholine and the overactivity of its degrading enzyme acetylcholine esterase at the NMJ. The impact of sleep deprivation on synaptic homeostasis in the brain has been extensively reported recently. The present evidence from our studies shows new information on the role of sleep on the NMJ homeostasis and its functioning.

Dissimilar Anxiety-like Behavior in Prepubertal and Young Adult Female Rats on Acute Exposure to Aluminium.

BACKGROUND: Puberty is a developmental transition in which an estrogenic surge occurs, mediating the release of xenoestrogens, like aluminium. Aluminium's effect on anxiety in rodents at the different developmental stages is inconsistent. AIMS: This study aimed at investigating the effect of the metalloestrogenic property of aluminium on anxiety-like behavioral changes in prepubertal and young adult female rats. OBJECTIVE: Considering this aim, our objective was to evaluate the anxiety-like behavior by the elevated plus maze in prepubertal and young adult female rats with or without acute exposure to aluminium. METHODS: To address this property of aluminium, 5mg/Kg body weight (Al-5) and 10 mg/Kg body weight (Al-10) of aluminium was administered intraperitoneally to female rats at two developmental stages, prepubertal (PP; n = 8 for each dose) and young adult (YA; n = 6 for each dose) for two weeks. Post-treatment, three days behavioral assessment of the rats was done employing elevated plus maze. RESULTS: Reduced escape latency was seen in Al-5, Al-10 pre-pubertal rats, and Al-5 young-adult rats on day 3. A significant reduction in open arm time was seen in the Al-5 young-adult rats. Aluminium treatment in the pre-pubertal rats reduced their head dipping and grooming. Reduced sniffing, head dipping, and stretch-attended posture in the treated young-adult female rats showed that they had impaired risk-taking tendency. CONCLUSION: Differential effect on the anxiety-like behavior in the pre-pubertal and young-adult female rats might be due to the metalloestrogenic property of aluminium, acting differently on the two age groups.

Muscle temperature is least altered during total sleep deprivation in rats.

It has often been said that the brain is mostly benefitted from sleep. To understand the importance of sleep, extensive studies on other organs are too required. One such unexplored area is the understanding of muscle physiology during the sleep-wake cycle. Changes in muscle tone with different sleep phases are evident from the rapid eye movement sleep muscle atonia. There is variation in brain and body temperature during sleep stages, the brain temperature being higher during rapid eye movement sleep than slow-wave sleep. However, the change in muscle temperature with different sleep stages is not known. In this study, we have implanted pre-calibrated K-type thermocouples in the hypothalamus and the dorsal nuchal muscle, and a peritoneal transmitter to monitor the hypothalamic, muscle, and body temperature respectively in rats during 24 h sleep-wake cycle. The changes in muscle, body, and hypothalamic temperature during total sleep deprivation were also monitored. During normal sleep-wake stages, the temperature in the decreasing order was that of the hypothalamus, body, and muscle. Total sleep deprivation by gentle handling caused a significant increase in hypothalamic and body temperature, while there was least change in the muscle temperature. The circadian rhythm of the hypothalamic and body temperature in the sleep-deprived rats was disrupted, while the same was preserved in the muscle temperature. The results of our study show that muscle atonia during rapid eye movement sleep is a physiologically regulated thermally quiescent muscle state offering a conducive environment for muscle rest and repair.

Changes in sleep-wake cycle after microinjection of agonist and antagonist of endocannabinoid receptors at the medial septum of rats.

The role of medial septum in the genesis of slow-wave sleep and the inhibition of rapid eye movement sleep has been established using neurotoxic lesion and chemical stimulation of the medial septum. Intracerebroventricular injection of endocannabinoids (anandamide) decreases wake and increases slow-wave and rapid eye movement sleep in rats. Central cannabinoid (CB1) receptors are localized in the rat medial septum; however, the role of cannabinoid receptors at the medial septum on the regulation of sleep-wakefulness in rats lacks evidence. In this study, we have examined the changes in sleep architecture of 21 male Wistar rats, divided into three groups. Initially, 6 rats were used for dose standardization. Subsequently, one group (n = 6) was microinjected with CB1 receptor agonist, R-(+)-WIN 55,212-2 mesylate salt, the second group (n = 6) received microinjection of CB1 receptor antagonist LY 320,135, and the third group (n = 5) was microinjected with the vehicle, DMSO at the medial septum using stereotaxy. The sleep-wake cycle was recorded using electroencephalogram, electro-oculogram, and electromyogram. Microinjection of CB1 receptor agonist at the medial septum decreased slow-wave sleep and increased total sleep time. The increase in total sleep time was due to an increased percentage of rapid eye movement sleep. After the third and fourth hour of CB1 receptor antagonist microinjection at the medial septum, slow-wave sleep decreased when compared to vehicle injection, while rapid eye movement sleep decreased compared to baseline. We conclude that the endocannabinoid system at the septal nucleus acts through CB1 receptors to increase rapid eye movement sleep in rats.

Cortex senses environmental temperature earlier than the hypothalamus in awake rats.

Simultaneous and direct recording of temperature from the body, hypothalamus, and cortex in animals exposed to acute thermal challenges lack evidence. This study was conducted to assess the usual concept, that brain temperature is rather stable when animals are exposed to different ambient temperatures. In this study, we report the characteristic changes in the body, hypothalamic, and cortical temperature, when the rats were acutely exposed to cold (6 °C) and hot (36 °C) ambient temperature. The results of our study show that the body temperature is robustly regulated while hypothalamic and cortical temperatures vary on challenges to ambient cold (6 °C) and warm (36 °C) exposure in awake rats. The onset of response was observed quickest in the cortex, indicating that the cortical thermal sensing may relay intracranial thermal input to the hypothalamus for the regulation of body temperature within narrow limits. The present findings contradict earlier evidence, which stated that the brain does not participate in thermal sensing.

Effects of NMDA and non-NMDA ionotropic glutamate receptors in the medial preoptic area on body temperature in awake rats.

Glutamate when microinjected at the medial preoptic area (mPOA) influences brain temperature (Tbr) and body temperature (Tb) in rats. Glutamate and its various receptors are present at the mPOA. The aim of this study was to identify the contribution of each of the ionotropic glutamatergic receptors at the mPOA on changes in Tbr and Tb in freely moving rats. Adult male Wistar rats (n=40) were implanted with bilateral guide cannula with indwelling styli above the mPOA. A telemetric transmitter was implanted at the peritoneum to record Tb and locomotor activity (LMA). A precalibrated thermocouple wire implanted near the hypothalamus was used to assess Tbr. Specific agonist for each ionotropic glutamate receptor was microinjected into the mPOA and its effects on temperature and LMA were measured in the rats. The rats were also microinjected with the respective ionotropic receptor antagonists, 15min prior to the microinjection of each agonist. Amongst amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-d-aspartate (NMDA) and kainic acid, AMPA increased Tb and LMA when injected at the mPOA. Specific antagonists for AMPA receptors was able to attenuate this increase (p<0.005). Pharmacological blockade of NMDA was able to lower Tbr only. Microinjection of kainic acid and its antagonist had no effect on the variables. The finding of the study suggests that activation of the AMPA receptors at the mPOA, leads to the rise in body temperature.

L-glutamate microinjection in the preoptic area increases brain and body temperature in freely moving rats.

The role of the preoptic area (POA) in thermoregulation is well documented. Microinjection of various neurotransmitters into the POA in rats has been shown to influence body temperature. Alhough there are reports showing changes in temperature on administration of L-glutamate into the POA, the role of this excitatory amino acid in thermoregulation has not been studied in unanaesthetized rats. In the present study, brain and body temperatures were recorded in freely moving adult male Wistar rats with K-type thermocouple implanted near the hypothalamus and temperature transmitter implanted inside the peritoneum. Recordings were performed 2 h preinjection and 4 h postinjection. L-glutamate (0.14 nM) microinjection into the POA induced long-lasting hyperthermia and reduced locomotor activity. The rats remained curled up and showed piloerection. L-glutamate-induced hyperthermia was attenuated by previous injection of the ionotropic L-glutamate receptor antagonist, kynurenate (0.11 nM). We propose that L-glutamate in the POA participates not only in heat production and conservation but also plays a role in interlinking sleep and thermoregulation.

Cervical necrotizing fasciitis with descending mediastinitis: literature review and case report.

Cervical necrotizing fasciitis (CNF) can develop from odontogenic infections that spread to the deep fascial planes of the neck. This polymicrobial infection is rapidly progressive, destructive, and often fatal. Prompt diagnosis, recognition of acuity, aggressive, repeated surgical treatment, and medical management contribute to improved survival. Nevertheless, the progression of the disease to descending mediastinitis and septic shock leads to a poor prognosis and decreased survival. A comprehensive review of the current data regarding CNF was conducted using MEDLINE, PubMed, Scopus, and Google Scholar. The diagnostic elements, comorbid conditions, treatment modalities, complications, and survival rates were analyzed. CNF has a reported mortality rate of 7% to 20%, depending on the extent of neck involvement. When the disease progresses into the thorax, such as in the subset of patients with CNF complicated by descending necrotizing mediastinitis (DNM) of odontogenic origin, the mortality rate increases to 41%. This is greater than the reported mortality rate of 22% for DNM in cardiothoracic studies. When DNM is present, the risk of developing septic shock appears to be much greater, 22% versus 7%. In the presence of CNF, DNM, and sepsis, the mortality rate increases to 64%. Those who survive CNF complicated by DNM and sepsis have truly beaten the odds. CNF is an uncommon, but potentially fatal, condition that oral and maxillofacial surgeons might be called on to manage emergently. Treatment includes surgery and medical intensive care. Surgeons offer the best odds of patient survival by following these basic principles: airway security, early aggressive incision and drainage plus debridement with thoracotomy, as needed, close surveillance with computed tomography, and a low threshold for retreatment. In immunocompromised patients, even greater vigilance is required. Antibiotic therapy should be adjusted as cultures and sensitivities become available. Advances in interventional radiology might lead to improved survival by allowing guided minimally invasive drainage in critically ill patients who cannot tolerate additional surgical insult. Despite the technologic advances in diagnosis and treatment, CNF complicated by DNM mediastinitis and sepsis still results in astoundingly high mortality.