Open Access Systematic Review Article
Background: Vitamin C is an important plasma water-soluble antioxidant that plays an essential role in the absorption of iron, detoxification of exogenous compounds, and remaking vitamin E for the protection of lipid membranes. In addition, vitamin C is essential in the synthesis of collagen. Vitamin C concentrations of plasma are determined by dietary intake and genetic factors. Ascorbic acid is the functional form of vitamin C, which is transported into the cell through sodium vitamin C transporters (SVCTs). There are two forms of SVCTs which are SVCT1 encoded by the SLC23A1 gene and SVCT2 encoded by the SLC23A2. The SLC23A2 gene locus on human chromosome 20P12. It expresses in most human tissues, except lung and skeletal muscle that it is important in regulating the intracellular concentration of ascorbic acid to protect the cell from oxidative stress and promote type 1 collagen maturation. Maintaining proper concentrations of plasma and cellular vitamin C concentration is important for the normal metabolic function of the body and preventing several diseases. In the contrast, a low concentration of vitamin C caused by SLC23A2 variation can cause several chronic diseases. Our systematic review discusses four diseases related to the variation of SLC23A2 gene and plasma vitamin C levels which are glaucoma, acute coronary syndrome among women, gastric cancer, and HPV16-associated head and neck cancer.
Methods: By using NCBI databases, specifically GenBank to analyze DNA sequence and mRNA sequence of SLC23A2 gene. GenBank file format was helpful to extract an accession number of the gene, number of amino acids, number of exons and introns, and length of nucleotides. FASTA format was also useful to retrieve the nucleotide sequence and get the function of the protein. BLAST was used to compare the protein product of the SLC23A2 gene between humans and Macaca mulatta (Rhesus monkey).
Results: the accession number of the SLC23A2 gene was NC_000020.11, the number of exons found was 18, and the gene was located in chromosome 20. This gene encodes one of the two required transporters, and the encoded protein accounts for tissue-specific uptake of vitamin C. This gene had an official symbol of SLC23A1. And they found a significant association between the single-nucleotide polymorphism (SNP) rs1279683 (A > G) in SLC23A2 and an increased risk of POAG in homozygous G allele (GG) carriers. Also, POAG patients with this SNP appear to have a significantly lower level of plasma vitamin C compared to other genotypes. Finally, many organisms have the same gene, such as dogs, mice, rats, and chickens.
Conclusion: there is a significant association between SLC23A2 gene mutation, increased risk for vitamin C deficiency, and several diseases. SNP in the SLC23A2 gene was significantly associated with a higher risk of POAG in GG allele carriers as well as lower plasma vitamin C concentration.
Open Access Original Research Article
Background: Previous studies using basal insulin documented the lowest daily dose and least hypoglycemic events when combined with Glimepiride and Metformin while attaining desirable glycemic control. However, Pivotal trials with Soliqua excluded Glimepiride as a part of therapy as well as subjects with moderate obesity (BMI > 35kg/m2). Moreover, these trials were relatively short term.
Objective: Assess long term efficacy and safety of Soliqua in combination with Glimepiride and Metformin in subjects with type 2 diabetes irrespective of BMI in ‘real world’ experience.
Subjects: 30 adults with type 2 diabetes, age range 32-72 years with HbA1C >7.5% while receiving therapy with 1) Glimepiride, Metformin and Basal insulin and 2) Metformin and/or DPP 4 inhibitors and/or other SUs and /or GLP1 RA and/or Basal insulin and/or prandial insulin. Type 2 diabetes was confirmed by presence of C-peptide. Subjects with history of gastroparesis, Triglycerides over 300 mg/dl and pancreatitis were excluded. Subjects with elevated liver enzymes, over 2.5 times normal and EGFR < 30 ml/min were excluded as well.
Methods: All prior therapies were discontinued. All subjects were started on Glimepiride 8 mg, Metformin 1000-2000 mg and SC Soliqua was initiated prior to breakfast with daily dose 15 or 30 units as recommended. Daily dose was increased by 2 units every 3 days until AM fasting plasma glucose of 80-130 mg/dl was attained or the dose of 60 units was reached. The stable daily dose of Soliqua was continued until the time of analysis. Comparisons were conducted between body weights (kg), fasting plasma glucose (FPG) and HbA1C prior to initiation of combination therapy (pre Rx) and every 3-6 months until the time of analysis (post Rx).
Results: BMI ranged between 22-67 kg/m2. Duration of diabetes was 5-25 years. Duration of therapy with the combination therapy range, 7-56 months. Subjects were divided into 2 groups according to desirable HbA1C levels as per recommendations by ADA: 1) desirable HbA1C is < 7.0%, 2) desirable HbA1C 7-8 %. Both Fasting plasma glucose (mg/dl) and HbA1C (%) declined from 167 ± 10 and 9.7 ± 0.8 to 114 ± 4 and 7.6± 0.3 at the time of analyses (post Rx) respectively in the whole cohort. In 4 (0.13 %) morbidly obese subjects, FPG and HbA1C levels declined though not achieving desirable glycemic goals despite receiving maximal daily dose, 60 units of Soliqua. All four belonged to group 1. In the remaining 17 subjects desirable glycemic levels were attained and maintained. In group 2, desirable glycemia was reached in all 9 subjects. Symptomatic hypoglycemic events confirmed by blood sugar <70 mg/dl were reported by 4 subjects, none requiring secondary assistance. No severe hypoglycemia was reported. Mean daily dose of Soliqua was lower when compared to the pivotal trials.
Conclusion: Soliqua is effective and safe in the long term in all subjects irrespective of BMI when administered in combination with Glimepiride and Metformin. Moreover, lesser daily dose required to attain desirable glycemia with this oral combination may render it to be effective without attaining maximum daily dose in subjects with higher BMIs documented in pivotal trials using Metformin alone.
Open Access Original Research Article
This study determined the effect of oral administration of aqueous extract from Thyme (Thymus vulgaris) extract (TVE) on the antioxidant status and activity of some penile function enzymes (acetylcholinesterase (AChE), phosphodiesterase-5 (PDE-5), adenosine diaminase (ADA), and arginase) activity in normal and 5- Fluorouracil- induced oxidative stressed rats. Sixty adult Wister rats (210-225)g were divided into ten (10) groups (n=6): Group 1: received oral administration of normal saline (NC), Group 2: received 100 mg/kg of thyme extract orally (TE 100 mg/kg), Group 3: received 200 mg/kg of thyme extract orally (TE 200 mg/kg), rats in group four were treated with 400 mg/kg of thyme extract orally (TE 400 mg/kg), Those in group 5: received 25 mg/kg of Vitamin C orally, while group 6 to 10 were induced with 150 mg/kg of 5-Fluorouracil solution (5-FLU, i.p), but group 7-10 were treated 100 mg/kg, 200 mg/kg, 400 mg/kg and Vitamin C (25mg/kg), respectively. After fourteen (14) days of treatment, the rats were sacrificed and the penile tissue was carefully isolated and prepared into homogenate, which was used for antioxidant and enzymes biochemical analysis. The result revealed that i.p induction of 5-FLU caused a significant increase in malondialdehyde level, as well as AChE, ADA, PDE-5 and arginase activities wth concomitant decrease in thiol level when compared to control rats. However, the administration of TVE was found to reverse the effect of 5-FLU. The TVE was also found the reduced MDA level and all the enzyme activities, but boosted the thiol level in the normal rats when compared to control rats. Interestingly the effect of the TVE was found dose-dependently, and 400 mg/kg TVE was found to be more potent among all the doses used in both normal and 5-FLU-induced oxidative stress rats.
Open Access Original Research Article
The effects of Fleurya aestuans leaves and tetrahydroxyflavone on the reproductive functions of lead acetate induced testicular toxicity in Wistar rats was investigated in this study. The study animals were divided into control group (A) and toxicity-induced groups (B, C, D, E, F, and G). To determine all particulate parameters under inquiry, the study used established procedures. Histological and tissue biochemical studies were performed on the testes and caudal epididymis. The most active compound in the extract was found to be tetrahydroxyflavone, and treatment of the extract resulted in a significant (P<0.05) improvements in male mating behaviors, conceptive hormones, sperm parameters, and testicular biochemical parameters. The frequency of mount, intromission and ejaculation rose significantly (P<0.05), but the latencies of mount, intromission, and ejaculation, decreased. Similarly, the treatment of the extract with tetrahydroxyflavone reversed the harmful effects of lead acetic acid on various organ systems in the research animals, such as the epididymis and testes. As a result, the study recommends that Fleurya aestuans leaves be used to treat reproductive problems. The dose in human being experiment may be beneficial to patients with reproductive problems.