Determine the pharmacokinetics (half-life, volume of distribution and clearance) of AMB-FUBINACA in rats plasma using GC-MS / MS.

BACKGROUND: Several novel synthetic cannabinoids, including methyl 2-(1-(4-fluorobenzyl)-1Hindazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA), have recently surfaced on the illicit drug market. To determine the pharmacokinetic properties (half-life, volume of distribution, and clearance) of AMB-FUBINACA in rats plasma, a straightforward, quick, and highly sensitive analytical approach was developed. METHODS: Eighteen Wistar rats were divided into two groups: one control (saline vehicle) and one treatment group (AMB-FUBINACA at 50 mg/kg). Blood samples (400 µL) were withdrawn via catheters immediately before (t = 0) and at 30, 60, 90, 120, and 240 min following injection. Samples were collected into 1 mL tuberculin syringes, then transferred to 1.5 mL plastic tubes containing 5 µL of 1000 IU/mL K3-EDTA (Thomas Scientific). Place the EDTA tubes containing samples in a centrifuge and spin at 1000 g for 10 min at 4 °C. The top layer is the plasma fraction, which is decanted into cryovials and stored at -20 °C until analysis. The gas chromatography tandem mass spectrometry (GC-MS/MS) method was optimized and validated, combined with liquid-liquid extraction, to analyze AMB-FUBINACA in rat plasma. RESULTS: The research method successfully met the validation requirements set by the FDA, demonstrating selectivity and linear calibration curves within a concentration range of 0.5-1000 ng/ml. The correlation coefficient (r2) was determined to be 0.99, indicating a strong linear relationship. The analyte's limit of quantitation (LOQ) was determined to be 1-5 ng/mL. Subsequently, the method was successfully applied to investigate the pharmacokinetics of AMB-FUBINACA in rats' blood samples. Following oral administration, AMB-FUBINACA was rapidly absorbed, with a plasma half-life (t1/2) of 5.91 h, a volume of distribution (Vd) of 203.13 l, and a plasma clearance of 23.81122 L/h. CONCLUSION: These findings contribute to the understanding of AMB-FUBINACA's pharmacokinetics and pharmacodynamics.

Recent Advances in Analytical Techniques for Antidepressants Determination in Complex Biological Matrices: A Review.

Depression is one of the most prevalent but severe of mental disorders, affecting thousands of individuals across the globe. Depression, in its most extreme form, may result in self-harm and an increased likelihood of suicide. Antidepressant drugs are first-line medications to treat mental disorders. Unfortunately, these medications are also prescribed for other in- and off-label conditions, such as deficit/hyperactivity disorders, attention disorders, migraine, smoking cessation, eating disorders, fibromyalgia, pain, and insomnia. This results in an increase in the use of antidepressant medications, leading to clinical and forensic overdose cases that could be either accidental or deliberate. The findings revealed that people who used antidepressants had a 33% greater chance of dying sooner than expected, compared to those who did not take the medications. Analytical techniques for precisely identifying and detecting antidepressants and their metabolic products in a variety of biological matrices are greatly needed to be developed and made available. Hence, this study attempts to discuss various analytical techniques used to identify and determine antidepressants in various biological matrices, which include urine, blood, oral fluid (saliva), and tissues, which are commonly encountered in clinical and forensic science laboratories.

Arsenic Exposure through Dietary Intake and Associated Health Hazards in the Middle East.

Dietary arsenic (As) contamination is a major public health issue. In the Middle East, the food supply relies primarily on the import of food commodities. Among different age groups the main source of As exposure is grains and grain-based food products, particularly rice and rice-based dietary products. Rice and rice products are a rich source of core macronutrients and act as a chief energy source across the world. The rate of rice consumption ranges from 250 to 650 g per day per person in South East Asian countries. The source of carbohydrates through rice is one of the leading causes of human As exposure. The Gulf population consumes primarily rice and ready-to-eat cereals as a large proportion of their meals. Exposure to arsenic leads to an increased risk of non-communicable diseases such as dysbiosis, obesity, metabolic syndrome, diabetes, chronic kidney disease, chronic heart disease, cancer, and maternal and fetal complications. The impact of arsenic-containing food items and their exposure on health outcomes are different among different age groups. In the Middle East countries, neurological deficit disorder (NDD) and autism spectrum disorder (ASD) cases are alarming issues. Arsenic exposure might be a causative factor that should be assessed by screening the population and regulatory bodies rechecking the limits of As among all age groups. Our goals for this review are to outline the source and distribution of arsenic in various foods and water and summarize the health complications linked with arsenic toxicity along with identified modifiers that add heterogeneity in biological responses and suggest improvements for multi-disciplinary interventions to minimize the global influence of arsenic. The development and validation of diverse analytical techniques to evaluate the toxic levels of different As contaminants in our food products is the need of the hour. Furthermore, standard parameters and guidelines for As-containing foods should be developed and implemented.

Determination of in vitro human whole blood-to-plasma ratio of THJ-018 utilizing gas chromatography-Mass spectrometry.

OBJECTIVES: This study was aimed to determine in vitro human whole blood-to-plasma ratio (KWB/P) of THJ-018 by gas chromatography/mass spectrometry (GC/MS). MATERIALS AND METHODS: The samples (human blood) were sprayed with THJ-018 and an internal standard and extracted using solid-phase extraction. THJ-018 was determined in the final extracts by GC/MS. RESULTS: The value for KWB/P was 1.56 (1.38-1.81), and red blood cell partitioning was 1.01 (1.01-1.02). The distribution of THJ-018 between whole blood and plasma was observed to be affected by temperature. CONCLUSION: The data analysis supports the proposition that the ratio of the plasma to whole blood concentrations (1.56) is a suitable parameter characterizing THJ-018 distribution in whole blood. For toxicological analysis, it would be best to refrain from converting any drug concentration measured in whole blood to that anticipated in plasma or serum; however, toxic and therapeutic concentrations should be determined for the individual specimens collected.

Upregulated histone deacetylase 2 gene correlates with the progression of oral squamous cell carcinoma.

BACKGROUND: Histone deacetylases (HDACs) are considered as an essential regulator of cellular proliferation, differentiation, and apoptosis. The HDAC2 enzyme of Class I HDACs plays an important role in tumor progression of human malignancies. OBJECTIVE: The aim of the present study was to analyze the HDAC2 gene expression in pre-oral cancer and oral squamous cell carcinoma (OSCC), and its association with clinico-pathological features. METHODS: The HDAC2 protein expression was analyzed through the immunohistochemistry and western blot techniques in 82 oral pre-malignant, 90 OSCC, and 16 normal control tissues. qRT-PCR was used to quantify the mRNA fold change in all groups. RESULTS: The HDAC2 protein and mRNA levels were significantly higher in OSCC and pre-oral cancer groups compared to the controls. Immunostaining of HDAC2 protein was enhanced in 84.4% of OSCC and 67.1% of pre-cancerous tissue sections (p< 0.01). The mean protein level was analyzed as 1.96 ± 0.44 in oral carcinoma, 1.61 ± 0.39 in pre-cancer and 0.96 ± 0.10 in control tissues. In addition, HDAC2 mean protein level was associated with histological differentiation (OR = 25, p< 0.05) and tumor-node-metastasis (TNM) stages (OR = 6.2, p< 0.05) of OSCC patients. CONCLUSIONS: The upregulated HDAC2 gene in pre-cancer and OSCC tissues indicates its crucial role in the transformation of pre-malignant to malignant carcinoma. It could be a potential cancer biomarker of prognosis and targeted therapy in OSCC.

The maxillofacial injuries: A postmortem study.

OBJECTIVES: The aim of our study is to evaluate the incidence and etiology of maxillofacial fractures in autopsy cases of KGMU, Lucknow. MATERIALS AND METHODS: The sample consisted of 444 autopsy cases with maxillofacial injuries, who were brought to the mortuary of KGMU, Lucknow, for postmortem in the last year. Parameters such as gender, age, cause, type, and site of injury are evaluated. RESULT: The results of this study show that road traffic accidents are the main reason for maxillofacial injuries in the deceased, followed by railway accidents. Maxillofacial injuries are more common in adult males than in females. Majority cases also involved maxilla and zygomatic along with mandible. The most common type of facial fracture was Le Fort-2 fracture. CONCLUSION: Maxillofacial injuries are commonly seen in adult males, due to RTA, involving maxilla, zygomatic and mandible and presenting as Le Fort-2 fracture.

Role of dental expert in forensic odontology.

Forensic dentistry has become an integral part of forensic science over the past 100 years that utilizes dental or oro-facial findings to serve the judicial system. This has been due to the dedication of people like Gustafson's, Keiser-Nielson, and Suzuki for this field. They established the essential role which forensic dentistry plays mainly in the identification of human remains. The tooth has been used as weapons and under certain circumstances, may leave information about the identity of the biter. Dental professionals have a major role to play in keeping accurate dental records and providing all necessary information so that legal authorities may recognize mal practice, negligence, fraud or abuse, and identity of unknown individuals. This paper will try to summarize the various roles of dental experts in forensic medicine.