Aims:Neuroinflammation complicates traumatic brain injury predisposing to long-lasting neurologic impairment. The aim of the present study was to test whether parenteral administration a small peptide mimic (SN..8) of the receptor- activating- region of the human serotonin 2A receptor (1-, 3- and 5-days) after traumatic brain injury suppresses hippocampal inflammation in the rat compared to a scrambled peptide sequence of the same eight amino acids. Methods:Adult male Sprague-Dawley rats were exposed to lateral fluid percussion (LFP)-induced, traumatic brain injury (TBI) vs. sham injury. An identical 2 mg/kg concentration of SN..8 vs LD..8 (scrambled peptide) was administered via intraperitoneal route 1-, 3- and 5-days after injury. Two weeks post injury, the bilateral hippocampal, dorsal and ventral brain regions were examined by RT-PCR for altered gene expression. Comparisons were made between TBI vs sham injury; and active vs scrambled peptide treatment. Results:Two weeks after injury, the novel SN..8 peptide (vs scrambled peptide) significantly reduced (more than 3-fold) CD68 mRNA relative expression in ventral hippocampus in adult male Sprague-Dawley rats subjected to TBI (N=22) (1.65 ± 0.83 vs 5.27 ± 4.1; P=0.012). Conclusion:These results suggest that the neuroprotective effects of SN..8 peptide may be due in part to its ability to substantially suppress subacute inflammation in the ventral hippocampus.
Aims:Behavioral pattern separation is a hippocampal-dependent component of episodic memory and a sensitive marker of early cognitive decline. Here we tested whether mild traumatic injury causes loss of pattern separation in the rat and for its prevention by a novel neuroprotective peptide fragment of the human serotonin 2A receptor (SN..8). Methods:Lateral fluid percussion was used to induce mild traumatic brain injury in male Sprague- Dawley rats. Rats were trained to distinguish between a stable vs unstable swim platform separated by increasing distances (4.5 vs 3.0 vs 1.5 feet) in a modification to the classic Morris water maze. Peptide SN..8 vs scrambled version of same amino acids (2 mg/kg) was administered via intraperitoneal route (1-, 3- and 5-days) after lateral fluid percussion or sham injury. Rats received three weeks of training and two weeks of testing before injury and were tested again at 2 and 5-weeks after injury. Results:There was a gradient of decreasing incorrect responses to the choice between (stable vs unstable platform) as the platform separation distance was increased from 1.5 to 3.0 to 4.5 feet consistent with behavioral pattern separation. Systemic administration of SN..8 peptide (vs scrambled) peptide was associated with statistically significant lower rate of incorrect responses (at both 4.5 feet and 3.0 feet platform separation) in traumatic brain-injured rats (but not in sham-injured rats) tested at 2-weeks post-injury. Five weeks after injury, the rats had largely recovered and exhibited a much lower overall rate of incorrect responses across both drug and injury subgroups. Conclusions:Introduction of an unstable platform (choice phase of the Morris water maze) at varying distances from the stable platform resulted in behavior having the hallmark of pattern separation. Our data are the first to suggest that systemic administration of (2 mg/kg) SN..8 peptide immediately after mild traumatic brain injury (lateral fluid percussion) appeared to protect against loss of behavioral pattern separation in the rat.
Over the past 25 years of studying type 2 diabetes mellitus, a working hypothesis has emerged to move the development of precision medicine for type 2 diabetes mellitus forward. Earlier studies using amplified genomic DNAs for genomic-wide searches of human genes have led many investigators astray. However, a recent study has taken a different approach, using next-generation RNA sequencing, revealing an essential down-regulation of two genes, TPD52L3 and NKX2-1 . The current compendium focuses on describing all of the important priciples to clarify the hypothesis from the beginning: insulin sensitivity and glucose effectiveness, genetics, free fatty acids, cell membranes, atomistic glucose and glucose transport, β-cell functions, membrane flexibility and (pre-) diabetes type 2. Furthermore, this study sheds light on the importance of considering membrane flexibility in the context of type 2 diabetes and questions the potential risk associated with using the term ‘insulin resistance’.
Background: Hypogonadism in adult men is a clinical and biochemical syndrome associated with low level of testosterone, which may adversely affect multiple organ functions and quality of life.It is closely related to the development of diabetes.This study was designed to determine the incidence of hypogonadism and related risk factors among men with type 2 diabetes (T2D).Patients and Methods: A total of 300 male patients diagnosed with T2D age from 30-70 years were enrolled in the study.Arabic version of the Androgen Deficiency in Aging Male (ADAM) questionnaire was employed to assess the androgen insufficiency in men.Hemoglobin A1c, FSH, LH, total and free testosterone, levels were measured by enzyme immunoassay.Results: T2D patients were divided into two groups: 48 (16%) patients with hypogonadism and 252 (84%) patients without hypogonadism.Multiple logistic regression analysis for factors affecting Hypogonadism among patients according to (total testosterone + ADAM +ve) versus those without hypogonadism it was found that age, random blood sugar, body mass index (BMI), Hb A1c are independent risk factors for the development of hypogonadism with odds ratio (0.95, 1, 1.1, 1.37) with p value (0.02, 0.03, 0. 03, 0.008) respectively.The ROC analysis of the accuracy of indices and cut off values for the studied total testosterone for predicting the hypogonadism according to total testosterone + ADAM score positive: The AUC was 0.98 «p-value <0.0001» with sensitivity 100% and specificity of 96.4% at Cut off value ≤ 12. Conclusion:Several risk factors of diabetes are associated closely with hypogonadism.Age, BMI, blood sugar, and Hb A1c are independent risk factors for the development of hypogonadism in male patients with T2D.
Objective: Among experimental animal models, horses are the most adaptable to exercise and this ability has been extensively studied.Research on equine exercise physiology is mostly focused on genetics, and few integrated studies have focused on equine metabolomics.This study were conducted to analyze metabolites in plasma, urine, and sweat samples collected from Jeju pony and thoroughbred horses before and after exercise.In this study, we analyze the various equine samples using NMR (nuclear magnetic resonance) spectroscopy.Methods: 1 H NMR spectroscopy analysis were conducted with equine plasma, urine, and sweat samples collected from Jeju pony and thoroughbred horses before and after exercise.Relative metabolite levels between three types of were compared under exercise stimuli and by breeds.Results: A total 26, 39, and 36 metabolites were identified in each of plasma, sweat, and urine samples, respectively, of both thoroughbred and Jeju pony.A total 3, 12, 15 metabolites were exclusively detected in plasma, sweat, and urine samples, respectively, and 15 metabolites were detected in all samples at the same time.In addition, total 8 and 5 metabolites were detected after exercise in plasma and urine samples.Additionally, we obtained 16, 6, and 30 metabolites in plasma, urine, and sweat by breeds.
Introduction: This study aimed to explore the impact of comorbid hyperuricemia on disease severity in Japanese patients with coronavirus disease 2019 .This retrospective cohort study included patients with COVID-19 between July 2020 and February 2021. Methods:We divided patients into mild, moderate, and severe groups according to the degree of disease severity.Clinical and biochemical parameters on admission and comorbidities were compared between the mild and severe groups. Results:We enrolled 146 patients in this study: 36 patients were allocated to the mild group, 96 to the moderate group, and 14 to the severe group.The male sex, age, body mass index (BMI), systolic blood pressure, pulse rate, white blood cell counts, levels of serum urea nitrogen and uric acid were significantly higher in the severe group than in the mild group (p<0.05),while lymphocyte counts and estimated glomerular filtration rate were significantly lower (p<0.05).As for comorbidities, malignant tumor, diabetes mellitus, hypertension, chronic kidney disease (CKD), hyperlipidemia, and hyperuricemia were associated with COVID-19 severity.Logistic regression analysis indicated that hyperuricemia was significantly positively associated with the severity of COVID-19 independent of age, sex, BMI, comorbidities of diabetes mellitus, and malignant tumor.However, the association between hyperuricemia and COVID-19 severity was eliminated by correction with hypertension or CKD. Conclusion:These data suggested that comorbidities of hyperuricemia may indicate an increased risk of COVID-19 progression.Furthermore, patients with hyperuricemia comorbidities may require careful and intensive multidisciplinary treatment for hyperuricemia and hypertension and/or CKD to prevent progression of COVID-19.
71 US respondents, ages 14-19, evaluated phrases about what to do to avoid overeating.The phrases were selected by two student researchers, one in middle school, one in elementary school, using artificial intelligence.The phrases were combined according an underlying experimental design, creating 24 vignettes, with each of the 71 respondents evaluating a unique set of vignettes, rating each vignette on 'for me versus not for me'.Clustering reveal three clearly different mind-sets about what is most relevant to the respondent; Mind-Set 1 focuses on exercise, Mind-Set 2 focuses on eating healthfully, Mind-Set 3 focuses on parental responsibility.The three mind-sets emerged clearly and dramatically, even though the respondents evaluated combinations of messages, some relevant, some not relevant. Demonstrating the Mind Genomics Process and Results for the Topic of 'Preventing Childhood Obesity'The process begins with a topic, namely childhood obesity.In the traditional Mind Genomics process, before the introduction of artificial intelligence through Idea Coach, it was the researcher's job to create four questions which tell a story.The researcher would be
Objectives:Traumatic brain injury (TBI) was associated with increased plasma agonist autoantibodies targeting the serotonin 2A receptor. Repeated TBI exposure is associated with high risk for neurodegenerative and neuropsychiatric complications. Here we tested a hypothesis that repeated TBI is associated with plasma agonist autoantibodies targeting more than one kind of catecholamine G-protein coupled receptor. Methods:Protein-A affinity chromatography was used to isolate the IgG fraction of plasma in forty-two middle-aged and older adults who had experienced one or more TBI exposures. The Ig (1/40th dilution=7.5 ug/mL) were tested for neurotoxicity in mouse neuroblastoma cells using an acute neurite retraction assay indicative of Gq11/IP3/Ca2+ and RhoA/Rho kinase signaling pathways' activation. Three different linear synthetic peptides corresponding to the second extracellular loop of the alpha 1A, alpha 2A or serotonin 2A receptors were used as target antigen in different enzyme-linked immunoassays. The second extracellular loop receptor peptides themselves (alpha 1A, alpha 2A) or a fragment (serotonin 2A) were tested for ability to prevent Ig-induced neurite retraction. Results:Patients who had experienced either repeated TBI (N=10) or a single TBI with a co-morbid autoimmune disease (N=5) were significantly more likely to harbor neurotoxic plasma autoantibodies targeting both alpha 1 adrenergic and serotonin 2A receptors vs. patients having only a single TBI. Ig-induced neurotoxicity was significantly prevented by co-incubation with either 850 nM prazosin (alpha 1 adrenergic receptor) and/or 500 nM M100907 (serotonin 2A receptor) antagonists. Alpha 1 adrenergic receptor and serotonin 2A receptor Ig immunoreactive level and titer were significantly increased in repeated TBI and single TBI/autoimmune patients (N=7-8) compared to age-matched TBI patients without neurotoxic plasma Ig (N=4). SN.8, a linear synthetic peptide corresponding to a conserved region of the second extracellular loop (ECL) of the serotonin 2A receptor completely prevented neurite retraction induced by repeated TBI plasma Ig. A repeated TBI patient harboring alpha adrenergic receptor AAB alone experienced prospective steep decline in cognitive function over two years. Conclusions:Repeated TBI and TBI with associated autoimmunity harbored more than one kind of neurotoxic catecholaminergic agonist GPCR autoantibody each associated with high risk for steep rate of cognitive decline. Specific immunoassays using the second extracellular receptor loop as target antigen are needed to detect each specific different GPCR autoantibody. A fragment of the second ECL of the serotonin 2A receptor (SN.8) neutralized Ig-induced neurotoxicity in repeated TBI or TBI with associated systemic autoimmunity.
Aims:Accelerated cognitive decline frequently complicates traumatic brain injury. Obesity and type 2 diabetes mellitus drive peripheral inflammation which may accelerate traumatic brain injury-associated neurodegeneration. The Zucker rat harbors G-protein coupled receptor agonist IgG autoantibodies and in vitro neurotoxicity caused by these autoantibodies was prevented by a novel synthetic fragment of the serotonin 2A receptor. The aim of the present study was to test whether genetic obesity manifested in Zucker diabetic fatty rat is associated with greater spatial memory impairment before and after mild traumatic brain injury compared to Zucker lean rats. Furthermore, we investigated whether these neurodegenerative complications can be lessened by administration of a novel putative neuroprotective peptide comprised of a fragment of the second extracellular loop of the serotonin 2A receptor. Methods:Age-matched lean and fatty diabetic Zucker rats were tested in the Morris water maze (spatial memory) prior to receiving a sham-injury or lateral fluid percussion (LFP) mild traumatic brain injury. Behavioral testing was repeated at 1-week, 1-month, and 3-month intervals following injury. A synthetic peptide consisting of a portion of the 5-hydroxytryptamine (serotonin) 2A receptor (2 mg/kg) (vehicle, or an inactive scrambled version of the peptide (2 mg/kg)) was administered via intraperitoneal route every other day for 7 days after sham or LFP injury to lean rats or 7 days before and after sham or LFP injury to fatty rats. Results:Mild traumatic brain injury impaired recall of spatial memory in fatty and lean rats. Zucker fatty rats subjected to sham-injury or mild TBI experienced a significantly greater longitudinal decline in recall of spatial memory compared to lean Zucker rats. A synthetic peptide fragment of the 5-hydroxytryptamine 2A receptor significantly enhanced acquisition of spatial learning and it appeared to strengthen recall of spatial learning (one-week) after sham injury in Zucker rats. Conclusions:These data suggest that the Zucker diabetic fatty rat is a suitable animal model to investigate the role of metabolic factor(s) in accelerated cognitive decline. A novel synthetic peptide comprised of a fragment of the second extracellular loop of the human serotonin 2A receptor appeared to have neuroprotective effects on both acquisition and recall of spatial memory in subsets of Zucker rats, with relatively greater benefit in sham-injured, lean Zucker rats.
Purpose: We aimed to assess the fracture rate in patients who were placed on a drug holiday (DH) after minimum adequate therapy versus those who continued therapy (CT) in a real-life setting. Methods: This is a retrospective cohort study conducted in a tertiary academic center. Inclusion criteria involved osteoporotic adults who received minimum adequate bisphosphonate therapy (≥ 3 years), otherwise, patients were excluded. Results: Of 1,814 charts randomly selected and reviewed, 272 patients met the inclusion criteria. In our cohort, females were 90.9%, White 50.0%, and African American 40.5%. A DH was initiated in 119 patients (43.8%). In the CT versus DH cohorts, the mean duration of therapy was 6.0 ± 2.6 versus 5.7 ± 2.3 years, total duration of follow-up 6.9 ± 2.9 versus 7.8 ± 2.7 years, and fractures occurred in 11.7% versus 9.2% respectively, not statistically different. The mean duration of follow-up after starting DH was 2.5 ± 1.9 years. Upon risk stratification using FRAX scoring, in the high-risk cohort, fragility fractures occurred in 16.5% (n=22/133) of the CT group versus 13.5% (n=7/52) of the DH cohort (P=0.66). In the lower risk cohort based on FRAX scoring, fragility fractures occurred in 7.1% (n=10/131) of the CT group versus 6.0% (n=4/63) of the DH cohort (P=1.0). Conclusion: In our cohort, continued drug therapy did not provide additional fracture protective benefits beyond the minimum adequate duration of therapy. A drug holiday after three to five years of treatment may be considered after review of risk factors for future fracture.
Background: Despite the availability of efficacious drugs, tuberculosis remains a major public health problem in low-and middle-income countries.This study was aimed to determine the prevalence of tuberculosis in Massawa Hospital, Eritrea.Methods: Laboratory and medical records of tuberculosis patients in Massawa Hospital were reviewed.All patients who did sputum exam by Xpert Gene from January 01, 2018 to May 1, 2021 in Massawa Hospital were enrolled in this study.Categorical variables were presented in percent, frequencies, Chi-square test, and odds ratio with 95% confidence interval.P value <0.05 was considered significant.Results: Sputum examination was done on 2178 patients and the prevalence of bacteriologically positive tuberculosis was 7%.Moreover, the prevalence of rifampicin resistant tuberculosis among the total tested and bacteriologically positive patients was 0.4% and 5.9% respectively.The main reason for sputum examination was presumptive diagnosis of tuberculosis (85.5%).Tuberculosis spondylitis (15.6%) and adenitis (13.6%) were found to be the most common types of extra pulmonary tuberculosis.The prevalence of tuberculosis in HIV patients was 5.2% and all started highly active antiretroviral therapy.Patients aged 15 to 24 years were having higher prevalence of tuberculosis (8.8%, 95%CI 0.68-4.72,OR-1.79).And, those from Ghelaelo subzone were having about two times higher prevalence of tuberculosis (9.9%, 95%CI 1.39-3.06,OR-2.06).Patients who had previous history of tuberculosis were having about five times higher prevalence of tuberculosis (27.5%, 95%CI 2.65-11.17.OR-5.4,p<0.001) and Rifampicin resistant tuberculosis (9.1%, p<0.002). Conclusion:The prevalence of tuberculosis and the multidrug resistant tuberculosis among the confirmed cases was comparatively increased than the average WHO estimates for Eritrea and similar to a study conducted in Nakfa subzone, Eritrea.The prevalence of tuberculosis in HIV patients was higher to the WHO estimates and previous studies in the country.Previous history of tuberculosis was significantly associated with the prevalence tuberculosis and multidrug resistant tuberculosis.Further prospective studies to evaluate the national prevalence of tuberculosis and rifampicin resistant tuberculosis are highly recommended.
South Asians, representing one quarter of the world’s population, have disproportionally high rates of obesity and cardiometabolic disease thus resulting an epidemic health crisis. This crisis could be the consequence of epigenetic effects exacerbated during the colonial-era famines resulting in a unique starvation-adapted physiology. Due to evolutionary mismatch in circumstances of abundance, this starvation-adapted physiology can become harmful. Evidence for this starvation adaptation in South Asians includes high body fat and unfavorable adipokines; low lean body mass; lower resting energy expenditure (compounded by lack of brown adipose tissue); greater insulin resistance and insulin response; exaggerated lipemic response to fat and sugar intake; less capacity to handle an overabundance of food; lower fat burning (oxidative capacity) and VO2max during aerobic exercise; and energy-conserving response to resistance exercise, as well as increased lipoprotein (a) levels. The Roma people, also of South Asian ancestry, may represent an interesting pre-colonial historical control. Physician and patient knowledge of this unique physiology in South Asians will promote a stronger physician-patient relationship and foster compliance with treatment.
107 respondents each evaluated 60 unique vignettes (combinations of two, three or four messages), dealing with descriptions of how a person with obesity might feel.The respondent rated each vignette on degree to which the vignette would provoke a feeling of 'cannot deal with it' (viz., strong anxiety).Deconstruction of the responses to the full set of 36 messages on a respondent-respondent basis revealed that two specific messages provoked the highest degree of anxiety; you believe that the food industry will work to help you find the right foods to eat and you just can't control the eating.Substantial differences emerged for age, and for the location where anxiety might be experienced (e.g., while listening to music.).Clustering the 107 respondents into mind-sets, groups with different points of view, revealed three radically different group, based on the elements which drive anxiety: MS1 -Anxiety about acceptance by others; MS 2 -Anxiety when thinking about professional help; MS3 -Anxiety about helplessness and being out of control.
Aim:The aim of the present study was to test whether conjugation of a synthetic peptide corresponding to a fragment of the second extracellular domain of the human serotonin 2A receptor substantially alters the in vivo pharmacodynamic blood pressure-lowering profile of the peptide in different hypertensive rat strains. Methods:Sertuercept (SCLLADDN) was synthesized and modified using pegylation or myristolation. The two different peptide conjugates were tested in male Zucker diabetic fatty rats for acute and long-lasting blood pressure-lowering effects following single intraperitoneal administration. The myristolated Sertuercept was administered intraperitoneally to female Zucker fatty and male spontaneously hypertensive rats (SHR) and blood pressure was monitored either using tail cuff measurement (female Zucker) or by telemetry (SHR) rats. Plasma immunoglobulin G obtained by Protein G affinity chromatography in 25-week-old female Zucker or male spontaneously hypertensive rats was tested for binding to a linear synthetic peptide corresponding to the second extracellular loop of the serotonin 2A receptor. A cohort of male Zucker diabetic fatty rats was randomized to seven weeks of once-weekly myristolated Sertuercept or scrambled peptide (injections) and the kidneys were examined histologically for differences in total kidney lesions or fibrosis. Results:Pegylated Sertuercept promoted substantial blood pressure-lowering lasting approximately 30-48 hours in male Zucker diabetic fatty rats. Blood pressure-lowering following a single injection of Myristolated Sertuercept was much longer-lasting (6-11 days) and it was effective in male Zucker diabetic fatty rats, male spontaneously hypertensive rats and in a subset of hypertensive female Zucker fatty rats. Seven weeks' treatment with once-weekly Myristolated Sertuercept (2mg/kg) was associated with significantly fewer kidney lesions and less interstitial fibrosis compared to scrambled peptide in 25-week-old male Zucker diabetic fatty rats. Male spontaneously hypertensive rats (4 of 4 tested) harbored plasma IgG which bound significantly to serotonin 2A receptor peptide, and a subset of female Zucker fatty rats harboring IgG were responsive to blood pressure-lowering from the myristolated Sertuercept peptide. Summary:Myristolated-Sertuercept, an epitope-specific peptide comprised of a portion of second extracellular loop of the human serotonin 2A receptor was safe, well-tolerated and effectively lowered blood pressure for one week or longer in two different strains of male hypertensive rats. These data provide proof-of-concept that once-weekly systemic drug administration is feasible to achieve not only long-lasting hypertension control, but also substantial renoprotection.
AimTraumatic brain injury (TBI) was associated with increased plasma serotonin 2A receptor (5-HT2AR) autoantibodies in adults who experienced neurodegenerative complications. We tested whether the baseline presence of plasma serotonin 2A receptor (5-HT2AR) autoantibodies was a significant predictor of the two-year rate of cognitive decline in middle-aged and older adult TBI.MethodsPlasma from thirty-five middle-aged and older adult veterans (mean 65 years old) who had suffered traumatic brain injury was subjected to protein-A affinity chromatography. One-fortieth dilution of the resulting immunoglobulin (Ig) G fraction was tested for binding (in ELISA) to a linear synthetic peptide corresponding to the second extracellular loop region of the human 5-HT2A receptor. All available patients completed baseline and two-year follow-up neurocognitive tests of memory (St Louis University Mental Status), processing speed (Digit Symbol Substitution Test) and executive function (Trails-making Test, Part B). Change in cognitive performance was computed as (two-year - baseline) raw test score.ResultsEighteen patients completed both baseline and two-year follow up neurocognitive tests. TBI patients harboring plasma 5-HT2AR autoantibodies at the baseline examination (n=13) did not differ significantly in their baseline clinical characteristics (age, education level) compared to TBI patients lacking baseline plasma autoantibodies (n=5). Plasma serotonin 2AR antibody-positive patients experienced a significantly greater post-baseline decline in performance on the St Louis University Mental Status test (P=0.0118) and in the Digit Symbol Substitution Test (P=0.011), but not in Trails-making Part B (P=0.129) compared to serotonin 2AR antibody-negative patients. In multivariable linear regression analyses that adjusted for age, baseline presence of plasma 5-HT2AR autoantibody was a significant predictor of the two-year rate of decline in memory, and processing speed. Binding of plasma autoantibody to the serotonin 2A receptor peptide in the enzyme linked immunosorbent assay was also significantly higher (at 1/160th titer of the protein-A eluate= 1 μg/mL IgG) in TBI patients harboring vs. those not harboring baseline plasma 5-HT2AR autoantibodies.ConclusionThese data suggest that plasma 5-hydroxytryptamine 2A receptor autoantibodies which were increased in approximately two-thirds of middle-aged and older adults following traumatic brain injury predicts rapid and substantial declines in cognitive function (memory and processing speed), independent of age.
Purpose: To evaluate 24 hour glycaemic profile using AGP in patients with type 2 diabetes who are eligible for meal replacement therapy over a period of 14 days.To assess whether a precise meal replacement plan as an add on to standard of care will make a difference in smoothening out post-prandial peaks and increasing time spent in the desired (70 mg/dl-180 mg/dl) range compared to baseline time in range and post-prandial blood glucose level.Methods: Patients were mounted with AGP asked to follow the regular diet for 6 days.On the 7 th day, based on the AGP report, the most troubled meal was replaced with protein rich, calorie counted, low-carb and fiber enriched meal supplement for the next 6 days.On day 14, the AGP data were collected. Results:The analysis of full cohort (n=566) showed reduction in eA1c and eAG by 11.9% (from 7.84% to 6.90%) and 15.10% (from 178.41 mg/dL to 151.47 mg/dL), respectively when regular meal diet was compared with the replaced meal diet.The average TIR was improved by 23.56% (from 41.38 to 51.13) in full cohort, post-intervention with replaced meal. Conclusion:The glycemic profile of patients with type 2 diabetes was improved by meal replacement therapy over period of 14 days.
Aims:The study was planned to evaluate the effect of Clomiphene Citrate (CC) treatment as compared to testosterone replacement for late onset hypogoandism in with type 2 Diabetes Mellitu. Methods:The study included 72 male patients with late onset hypogonadism (assessed by ADAM questionnaire, serum total testosterone and LH) and T2DM out of 250 patients screened.The subjects with serum testosterone in the range of 200-300 ng/dl and with serum Luteinizing hormone (LH) level ≤9.4 IU/ml were treated with Clomiphene Citrate 25 mg/day (Group 1 N= 40).Patients with serum testosterone levels less than 200 ng/dl and serum LH < 9.4 IU/ml received testosterone every month for 3 months (Group 2 N=32).The post treatment hormone estimation along with ADAM questionnaire value was evaluated 3 month after commencing treatment.Results: ADAM symptom scores were worse in group 2 (N=32) than group 1 (N= 40 ).There was a comparable increase in mean testosterone levels in both groups at 3 months (550.16± 85.05 vs 509.72 ± 39.18 ng/dl; p = 0.03).Mean ADAM scores also decreased significantly in both the groups. Conclusion:Treatment with clomiphene citrate in male patients with T2DM and hypogonadism showed improvement in both clinical and biochemical measures.The study suggested that clomiphene citrate might be considered as a safe and effective alternative treatment strategy for late onset hypogonadism in male patients with type 2 DM.
BackgroundThe previous studies of our research group indicate that the weakening of mitochondrial autophagy function is the key mechanism of obesityinduced insulin resistance, and Mitochondrial autophagy mediated by PINK1/Parkin pathway can reverse mitochondrial dysfunction.Recently, we found that FOXO3a, as an upstream regulator of PINK1, has been found to play a key role in regulating mitochondrial autophagy.However,FOXO3a is regulated by deacetylation. ObjectiveTo explore whether Modified Dachaihu Decoction can regulate liver mitochondrial autophagy mediated by the PINK1/Parkin signal pathway by regulating the expression of FOXO3a acetylation. MethodsEstablish cell models.They were divided into three groups (blank control group, model control group, and Modified Dachaihu Decoction group).The supernatant was extracted and determined by a biochemical method; The insulin sensitivity of each group was evaluated by a 3H-D-glucose incorporation test; MDA and TNFα、IL-6 in the supernatant were detected by ELISA level; The level of SOD was detected by spectrophotometry.The expression of mitochondrial autophagy-related proteins and the expression of FOXO3a and ace-FOXO3a were measured by Western blot. ResultsCompared with the model control group, the Modified Dachaihu Decoction group increased insulin sensitivity, and The levels of TNF-α、IL-6, and MDA decreased, while the activity of SOD increased (P < 0.05).Western blot showed that compared with the model control group, the expression of mitochondrial autophagy-related proteins and FOXO3a in the Modified Dachaihu Decoction group increased, and the expression of ace-FOXO3a decreased (P < 0.05). ConclusionsWe speculate that in this experiment, Modified Dachaihu Decoction may regulate mitochondrial autophagy mediated by PINK1/ Parkin signal pathway by downregulating the expression of FOXO3a acetylation, to reduce Hepatic Insulin Resistance in Obesity.
