Role of TREM2 in Alzheimer's Disease and its Consequences on ß- Amyloid, Tau and Neurofibrillary Tangles.

Alzheimer's Disease (AD) is age-related neurodegenerative disorder recognized by a steadily gradual cognitive decline that has devastating personal and socioeconomic implications. Recently, some genetic factors for AD have been identified which attracted wide attention of researchers in different areas of AD biology and possible new therapeutic targets. Alternative forms of triggering receptor expressed on myeloid cells 2 (TREM2) genes are examples of such risk factors, which contribute higher risk for developing AD. Comprehending TREM2 function pledge to provide salient insight into how neuroinflammation contributes to AD pathology. The dearth of microglial TREM2 shepherd to augmented tau pathology is couple with frequent enhancement of activated neuronal stress kinases. The involvement of TREM2 in the regulation of tau-associated innate immune response of the CNS has clearly demonstrated through these findings. However, whether decrease level of TREM2 assists pathology of tau through changed clearance and pathological escalation of tau or through direct contact between microglia and neuron and any alternative possible mechanisms need to examine. This review briefly summarizes distinct functional roles of TREM2 in AD pathology and highlights the TREM2 gene regulation. We have also addressed the impact of TREM2 on ß-amyloid plaques and tau pathology in Alzheimer's disease.

Berberine: A Plant-derived Alkaloid with Therapeutic Potential to Combat Alzheimer's disease.

Berberine (a protoberberine isoquinoline alkaloid) has shown promising pharmacological activities, including analgesic, anti-inflammatory, anticancer, antidiabetic, anti-hyperlipidemic, cardioprotective, memory enhancement, antidepressant, antioxidant, anti-nociceptive, antimicrobial, anti- HIV and cholesterol-lowering effects. It is used in the treatment of the neurodegenerative disorder. It has strong evidence to serve as a potent phytoconstituent in the treatment of various neurodegenerative disorders such as AD. It limits the extracellular amyloid plaques and intracellular neurofibrillary tangles. It has also lipid-glucose lowering ability, hence can be used as a protective agent in atherosclerosis and AD. However, more detailed investigations along with safety assessment of berberine are warranted to clarify its role in limiting various risk factors and AD-related pathologies. This review highlights the pharmacological basis to control oxidative stress, neuroinflammation and protective effect of berberine in AD, which will benefit to the biological scientists in understanding and exploring the new vistas of berberine in combating Alzheimer's disease.

Strategic use of nanotechnology in drug targeting and its consequences on human health: A focused review.

Since the development of first lipid-based nanocarrier system, about 15% of the present pharmaceutical market uses nanomedicines to achieve medical benefits. Nanotechnology is an advanced area to meliorate the delivery of compounds for improved medical diagnosis and curing disease. Nanomedicines are gaining significant interest due to the ultra small size and large surface area to mass ratio. In this review, we discuss the potential of nanotechnology in delivering of active moieties for the disease therapy including their toxicity evidences. This communication will help the formulation scientists in understanding and exploring the new aspects of nanotechnology in the field of nanomedicine.

Attenuation of Haemodynamic Parameters in Response to Pneumoperitoneum during Laparoscopic Cholecystectomy: A Randomized Controlled Trial Comparing Infusions of Propofol and Dexmedetomidine.

INTRODUCTION: Effective control of sympathetic response to pneumoperitoneum is vital to avoid morbidity in patients undergoing laparoscopic surgeries. This control must be achieved without any side effects of the drugs being used as well as ensuring a raid recovery from anaesthesia in order to maximise operation theatre utility. AIM: To study the effectiveness of dexmedetomidine in attenuating the haemodynamic response to pneumoperitoneum during laparoscopic cholecystectomy (using only the maintenance dose) with that of propofol and compare time to extubation, haemodynamics on extubation, sedation score after extubation and any incidence of side effects between the two study drug. MATERIALS AND METHODS: Sixty American Society of Anaesthesiologist (ASA) I and II patients undergoing laparoscopic cholecystectomy between age of 20-60 years were randomly divided into two groups of 30 patients each: Group D to receive dexmedetomidine in dose of 0.2-0.7 µg/kg/hr titrated as per clinical response and Group P to receive propofol in dose of 25-75 µg/kg/min (1.5-4.5 mg/kg/hr) titrated as per clinical response after standard anaesthetic induction. Data recording was done for changes in haemodynamic parameters, time to extubation and post extubation sedation score. Statistical analysis was done using student's-test and Chi-square test with p-value of< 0.05 was considered significant. RESULTS: Attenuation of haemodynamic parameters by dexmedetomidine during the intraoperative period even without the loading dose was comparable to that by propofol (p-value >0.05). Time to extubation was similar in both the groups (p-value >0.05). Haemodynamics on extubation was better controlled in dexmedetomidine group (p-value <0.05) while the sedation score was better in propofol group (p-value <0.05). Mean dose of dexmedetomidine and propofol used were 0.504±0.09 µg/kg/hr and 3.19±0.7 mg/kg/hr respectively. CONCLUSION: Dexmedetomidine in a dose of 0.2-0.7 µg/kg/hr provides a stable haemodynamics without any side effects in patients undergoing laparoscopic cholecystectomy.

Dexmedetomidine as an Additive to Spinal Anaesthesia in Orthopaedic Patients Undergoing Lower Limb Surgeries: A Randomized Clinical Trial Comparing Two Different Doses of Dexmedetomidine.

INTRODUCTION: Use of dexmedetomidine as an additive to spinal anaesthesia is gaining popularity; but there seems to be no clear consensus on the ideal dose to be used. Because of dose related prolongation of duration of motor blockade along with increase in the incidence of side effects of dexmedetomidine namely hypotension and bradycardia, use of higher doses is not recommended. AIM: To evaluate the efficacy of two different doses of dexmedetomidine (3 µg and 5 µg) given in combination with 0.5% hyperbaric bupivacaine via intrathecal route with regard to the quality of anaesthesia namely the time to attain highest sensory and motor blockade, side effects of dexmedetomidine and time to first rescue analgesia. MATERIALS AND METHODS: Sixty American Society of Anaesthesiologist (ASA) Grade I and II orthopaedic patients undergoing lower limb surgeries between the ages of 20-60 years and height >150 cm were randomly divided into two groups of 30 patients each: Group D3 to receive 3 µg of Inj. Dexmedetomidine (0.5 ml, reconstituted using normal saline) along with 12.5 mg (2.5 ml) of 0.5% hyperbaric bupivacaine and Group D5 to receive 5 µg of inj. Dexmedetomidine (0.5 ml, reconstituted using normal saline) along with 12.5 mg (2.5 ml) of 0.5% hyperbaric bupivacaine keeping the total volume of study drug constant in all 60 patients (3 ml). Data recordings were done for time to reach best sensory and motor block, intraoperative haemodynamic changes and time to first postoperative rescue analgesia. Statistical analysis was done using student's t-test and Chi-square test with p-value of <0.05 considered to be significant. RESULTS: The two groups analysed were similar in terms of demographic profile, time to reach highest sensory block (T10) dermatome, time to reach Bromage scale 4, time to surgical incision after spinal and the total duration of surgery (p>0.05). The change in haemodynamics was similar (p>0.05). A statistically significant difference (p<0.001) was observed in time to first rescue analgesia after skin closure with Group D3 having 206.47 minutes while in Group D5 the time was 271.33 minutes. CONCLUSION: Used in a dose of 5 µg (in 0.5 ml volume) as an additive in spinal anaesthesia maximal beneficial effect of dexmedetomidine can be obtained without any side effects.