Amelioration of Cytogenotoxic Damage in Drug Abusers Supplemented with Folic Acid.

BACKGROUND: Cytogenotoxic damage caused by the consumption of legal and illegal drugs in drug abusers has been demonstrated, primarily due to alterations in their antioxidant capacity, cellular repair mechanisms, and increased production of free radicals. Folic acid shows antioxidant activity by acting as a reducing agent, neutralizing present free radicals, and reducing genomic damage. METHODS: The intervention involved administering 15 mg of folic acid, divided into three doses per day, to a group of 44 drug abusers. The frequency of nuclear abnormalities (NAs) was determined; micronuclei (MNs), nuclear buds (NBUDs), binucleated cells (BNs), abnormally condensed chromatin (CC), karyorrhexis (KX), pyknotic nuclei (PNs), and karyolysis (KL) were determined at different pre-treatment (baseline) and post-treatment time points at 15 and 30 days. Additionally, a group of 44 healthy individuals was used as the control group. RESULTS: We observed a statistically significant decrease in the frequency of NAs in the drug abuser group (28.45 ± 17.74 before supplementation vs. 11.18 ± 7.42 at 15 days and 9.11 ± 10.9 at 30 days of supplementation). Specifically, it decreased the frequency of NBUDs, BNs, CC, KX, and PNs (p < 0.05). CONCLUSION: Our study demonstrates a clear improvement in cytogenotoxic damage in drug abusers supplemented with folic acid.

mtDNA Single-Nucleotide Variants Associated with Type 2 Diabetes.

Type 2 diabetes (T2D) is a chronic systemic disease with a complex etiology, characterized by insulin resistance and mitochondrial dysfunction in various cell tissues. To explore this relationship, we conducted a secondary analysis of complete mtDNA sequences from 1261 T2D patients and 1105 control individuals. Our findings revealed significant associations between certain single-nucleotide polymorphisms (SNPs) and T2D. Notably, the variants m.1438A>G (rs2001030) (controls: 32 [27.6%], T2D: 84 [72.4%]; OR: 2.46; 95%CI: 1.64-3.78; p < 0.001), m.14766C>T (rs193302980) (controls: 498 [36.9%], T2D: 853 [63.1%]; OR: 2.57, 95%CI: 2.18-3.04, p < 0.001), and m.16519T>C (rs3937033) (controls: 363 [43.4%], T2D: 474 [56.6%]; OR: 1.24, 95%CI: 1.05-1.47, p = 0.012) were significantly associated with the likelihood of developing diabetes. The variant m.16189T>C (rs28693675), which has been previously documented in several studies across diverse populations, showed no association with T2D in our analysis (controls: 148 [13.39] T2D: 171 [13.56%]; OR: 1.03; 95%CI: 0.815-1.31; p = 0.83). These results provide evidence suggesting a link between specific mtDNA polymorphisms and T2D, possibly related to association rules, topological patterns, and three-dimensional conformations associated with regions where changes occur, rather than specific point mutations in the sequence.

Ivermectin compared with placebo in the clinical course in Mexican patients with asymptomatic and mild COVID-19: a randomized clinical trial.

BACKGROUND: Despite the development and application of vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) around the world, the scientific community is still trying to find some therapies to avoid or ameliorate the fatal evolution of the Coronavirus disease 2019 (COVID-19). Since the publication of the potential use of ivermectin as a treatment against the disease, a pleiad of information about it has been published. However, the evidence is not strong or weak enough to conclude its usefulness in the clinical evolution of patients infected with SARS-CoV-2. We evaluate the efficacy and safety of ivermectin in the treatment of Mexican patients with asymptomatic and mild COVID-19 in a three-day administration in comparison to placebo. METHODS: A randomized, double-blind, placebo-controlled trial was carried out in 66 adults with asymptomatic and mild COVID-19. Patients were randomly assigned 1:1 ratio to ivermectin plus acetaminophen or placebo plus acetaminophen. The primary endpoint was the proportion of subjects without a disease progression to severity according to COVID-19 guidelines by the National Institutes of Health (NIH) since randomization to 14 days. RESULTS: None of the participants presented progression to a severe state in either group. Viral load was measured on Days 1, 5, and 14. No significant differences were observed in baseline or 14-day between groups (p = 0.720 and 0.362, respectively). However, on Day 5, a significant difference in viral load was observed between groups (p = 0.039). The frequency of symptoms was similar between groups, and no significant differences were observed. The most frequent symptom was cough. One severe adverse event associated with SARS-CoV-2 infection was observed in the ivermectin group. CONCLUSIONS: At standard doses, ivermectin is not effective to prevent progression to a severe state or reducing symptoms in adults with asymptomatic and mild COVID-19. Trial registration The study was registered with ClinicalTrial.gov (NCT04407507) on May 29, 2020.

Mitochondrial Control Region Variants Related to Breast Cancer.

Breast cancer has an important incidence in the worldwide female population. Although alterations in the mitochondrial genome probably play an important role in carcinogenesis, the actual evidence is ambiguous and inconclusive. Our purpose was to explore differences in mitochondrial sequences of cases with breast cancer compared with control samples from different origins. We identified 124 mtDNA sequences associated with breast cancer cases, of which 86 were complete and 38 were partial sequences. Of these 86 complete sequences, 52 belonged to patients with a confirmed diagnosis of breast cancer, and 34 sequences were obtained from healthy mammary tissue of the same patients used as controls. From the mtDNA analysis, two polymorphisms with significant statistical differences were found: m.310del (rs869289246) in 34.6% (27/78) of breast cancer cases and 61.7% (21/34) in the controls; and m.315dup (rs369786048) in 60.2% (47/78) of breast cancer cases and 38.2% (13/34) in the controls. In addition, the variant m.16519T>C (rs3937033) was found in 59% of the control sequences and 52% of the breast cancer sequences with a significant statistical difference. Polymorphic changes are evolutionarily related to the haplogroup H of Indo-European and Euro-Asiatic origins; however, they were found in all non-European breast cancers.

Class I MHC Polymorphisms Associated with Type 2 Diabetes in the Mexican Population.

Type 2 diabetes (T2D) has been linked to the expression of Human Leukocyte Antigens, principally to the Major Histocompatibility Complex Class II, with only scarce reports of Major Histocompatibility Complex Class I in specific populations. The objective of the present work was to explore the presence of polymorphisms in the MHC Class I related to T2D in the Mexican population using the Genome-Wide Association Studies Slim Initiative in Genomic Medicine of the Americas (GWAS SIGMA) database. This database contains information on 3848 Mexican individuals with T2D and 4366 control individuals from the same population without a clinical or hereditary history of the disease. The searching criteria considered a p-value of <0.005 and an odds ratio (OR) of >1.0. Ten novel, statistically significant nucleotide variants were identified: four polymorphisms associated with HLA-A (A*03:01:01:01) and six with HLA-C (C*01:02:01:01). These alleles have a high prevalence in Latin American populations and could potentially be associated with autoimmunity mechanisms related to the development of T2D complications.

Comparison of prevalence of diabetes complications in Brazilian and Mexican adults: a cross-sectional study.

BACKGROUND: Type 2 diabetes is more frequent in Latin American people than in non-Hispanic whites due to a combination of genetic and lifestyle risk factors. Brazil and Mexico are the most populous countries in Latin America. The present study aimed to compare the results of the National Health Survey "PNS" in Brazil and the National Survey Health and Nutrition "ENSANUT" in Mexico regarding the prevalence, complications and healthcare issues of diabetes in both countries. METHODS: A cross-sectional study was conducted with data from the National Health Survey (PNS) of 2013 in Brazil and the National Survey of Health and Nutrition (ENSANUT) of 2018 in Mexico. The prevalence of diabetes, complications and risk factors related to developing diabetes were considered. RESULTS: The respondents included 3636 individuals in Brazil and 4555 individuals in Mexico. There were significant differences in age and time living with diabetes between the two countries. Mexican people had twice as likely as Brazilian people to have a complication (p < 0.0001). The principal risk factor (OR 2.47; p ≤ 0.0001) for developing any diabetic complication was living with diabetes for more than 15 years. Visual impairment was the most frequent complication in both countries, but it was more prevalent in Mexico (p ≤ 0.001). CONCLUSIONS: Diabetes complications are important health problems in Brazil and Mexico. Visual impairment was the principal complication in both countries. Several factors, such as access to and type of health system, living in a rural area, treatment, BMI and performing preventive actions, affected the risk of developing a complication. However, living with diabetes for more than 15 years was the principal risk factor. National health surveys have added significant information on the impact of diabetes in these Latin American populations. This comparison of data could provide valuable information to guide national policies and program decisions in both countries.

Efficacy of clindamycin compared with amoxicillin-metronidazole after a 7-day regimen in the treatment of periodontitis in patients with diabetes: a randomized clinical trial.

OBJECTIVE: To determine the efficacy of clindamycin compared with amoxicillin-metronidazole after a 7-day regimen during nonsurgical treatment of periodontitis in patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: In this double-blind, randomized clinical trial, a total of 42 patients with chronic periodontitis and type 2 diabetes were included. Patients were randomly assigned to treatment with either clindamycin or amoxicillin-metronidazole three times a day during 7 days. Clinical determinations (probing depth, bleeding on probe, and plaque index) were performed to determine the extent and severity of periodontitis before and after the pharmacological treatment. RESULTS: After 7 days of administration of clindamycin or amoxicillin-metronidazole, no differences were observed between the clinical determinations, probing depth (0.44 vs 0.50 mm, p=0.624), plaque index (17.62 vs 15.88%, p=0.910), and bleeding on probing (16.12 vs 22.17%, p=0.163), respectively. There were no adverse events in either group. CONCLUSION: The administration during 7 days of clindamycin or amoxicillin/metronidazole showed the same efficacy for the reduction of probing depth, plaque index, and bleeding on probing in patients with periodontitis and type 2 diabetes.

The utility of genomic public databases to mitochondrial haplotyping in contemporary Mestizo population of Mexican origin.

There are different public databases and open access information that can be exploited to be reused in different research projects. With this concept in mind, we carried out a study to answer the question about the prevalence of haplogroups in human populations of modern Mexico. Since the publication of genomic and mitochondrial data in Latin American populations are very scarce and with very small samples, our work proposes to consider the availability of genomic and genetic data collections that can be reused for other purposes, different from those initially proposed in the investigations where the sequences were obtained. The objective of the present study was to explore the population structure of Mexico using available information in the public database. Through the search of information in the nucleotide database of National Center of Biotechnology Information (NCBI) of complete sequences of mitochondrial genome (16 Kb) of indigenous people, Mexican Mestizo population and Mexican-Americans living in the United States, they were classified according to the polymorphisms associated with haplogroups A, B, C and D reported in the literature as the most frequent. We obtained 283 sequences, of which 255 were selected with the criteria mentioned. The haplotyping results showed 113 different clades and subclades distributed in a general way in eight haplogroups. The most frequent groups that dominate the population were the haplogroup A with 90 individuals representing 36%, followed by haplogroup B in 65 individuals representing 26% of the sample.

Efficacy and Safety of 0.6% Pazufloxacin Ophthalmic Solution Versus Moxifloxacin 0.5% and Gatifloxacin 0.5% in Subjects with Bacterial Conjunctivitis: A Randomized Clinical Trial.

PURPOSE: The purpose of this study was to evaluate the clinical efficacy and safety of a novel ophthalmic solution of pazufloxacin on the ocular surface of patients with bacterial conjunctivitis after 7 days of intervention. METHODS: This is a phase 2, double-blind, controlled, multicenter, clinical trial of 300 subjects, randomized to either a 3 dosing regimen of pazufloxacin 0.6% ophthalmic solution (twice a day [BID], n = 90; 3 times a day [TID], n = 76; 4 times a day [QID], n = 68), moxifloxacin 0.3% TID (n = 82), or gatifloxacin 0.5% TID (n = 72). Follow-up was set on days 0, 3, and 7. Assessments of ocular signs were performed, both anterior and posterior segments. The primary outcome measures included conjunctival culture and clinical signs. Safety variables included adverse events (AEs), lisamine green, fluorescein ocular surface stains, and clinical signs of tolerability. RESULTS: After intervention, bacterial eradication was reported in all groups: pazufloxacin BID 79%, pazufloxacin TID 84%, pazufloxacin QID 84%, moxifloxacin 80%, and gatifloxacin 82%. There were no significant differences between treatments. Similar results were reported in clinical remission: pazufloxacin BID 89%, pazufloxacin TID 98%, pazufloxacin QID 92%, moxifloxacin 91%, and gatifloxacin 92% (P = 0.03 comparing pazufloxacin BID vs. TID). There were no differences between female and male responses. The AEs were not related to the interventions. CONCLUSIONS: A simplified dosing regimen was selected to follow the development of ophthalmic pazufloxacin based on its efficacy and safety profile. Pazufloxacin, 1 drop 3 times daily, showed similar rates of bacterial eradication and clinical remission compared with other fluoroquinolones.

Bioavailability of generic 0.05% difluprednate emulsion in the aqueous humor, cornea, and conjunctiva of New Zealand rabbits after a single dose compared with commercial difluprednate.

BACKGROUND: To determine the concentration after a single dose of generic 0.05% difluprednate and commercial difluprednate in the aqueous humor, cornea, and conjunctiva of New Zealand rabbits, a preclinical study in 72 male New Zealand white rabbits was performed. A single dose (50 µL) of two 0.05% difluprednate ophthalmic formulations was instilled in both eyes. Conjunctiva, cornea, and aqueous humor samples were collected at nine time points over 8 h (four animals per time point). The active metabolite of difluprednate, 17-difluoroprednisolone-butyrate (DFB), concentrations was quantified using HPLC. RESULTS: Measurable levels of DFB were quantified in all three ocular tissues. After a single instillation, the highest concentration of difluprednate was found between 30 and 60 min in the conjunctiva, cornea, and aqueous humor, respectively. There was no significant difference between both formulations in any tissue at any time point. After 3 h, no metabolites of either emulsion were found in any tissue. CONCLUSIONS: Difluprednate penetrates into different ocular tissues. Generic difluprednate has a similar pharmacokinetic profile compared with commercial difluprednate.

Bromfenac 0.09% bioavailability in aqueous humor, prophylactic effect on cystoid macular edema, and clinical signs of ocular inflammation after phacoemulsification in a Mexican population.

PURPOSE: The purpose of this study was to evaluate the aqueous humor bioavailability and clinical efficacy of bromfenac 0.09% vs nepafenac on the presence of cystoid macular edema (CME) after phacoemulsification. MATERIAL AND METHODS: A Phase II, double-blind, masked, active-controlled, multicenter, clinical trial of 139 subjects, randomized to either a bromfenac 0.09% ophthalmic solution (n=69) or nepafenac 0.1% (n=70). Subjects instilled a drop three times a day for a period of 30 days. Follow-up visits were on days 2, 7, 15, 30, and 60. Biomicroscopy, clinical ocular signs, and assessment of posterior segment were performed. The primary efficacy endpoints included the presence of CME evaluated by optical coherence tomography. Safety evaluation included intraocular pressure, transaminase enzymes, lissamine green, and fluorescein stain. RESULTS: The demographic and efficacy variables were similar between groups at baseline. The presence of pain, photophobia, conjunctival hyperemia, chemosis, cellularity, and corneal edema disappeared by day 30 in both groups. The central retinal thickness did not show significant changes after treatment when compared to baseline as follows: in the bromfenac group (247.2±32.9 vs 252.0±24.9 µm; P=0.958) and in nepafenac group (250.8±34 vs 264.0±34.1 µm; P=0.137), respectively. A statistically significant difference was observed between bromfenac and nepafenac group: (252.0±24.9 vs 264.0±34.1 µm; P=0.022), at day 30, respectively; even though there was no clinical relevance in the presentation of CME. There were no significant alterations in intraocular pressure, either lissamine green or fluorescein stains. The adverse events were not related to the interventions. CONCLUSION: Bromfenac 0.09% ophthalmic solution showed similar clinical efficacy to reduce the presentation of CME after phacoemulsification compared to nepafenac 0.01%.

Histopathological changes on the ocular surface of New Zealand white rabbits after instillation of a fixed combination of 0.09 % xanthan gum and 0.1 % chondroitin sulfate.

The aim of this study was to evaluate the histopathological changes in a model of New Zealand white rabbits after the ocular instillation of a fixed combination containing 0.09 % xanthan gum and 0.1 % chondroitin sulfate for 15 days. This was a preclinical study which compared the previously described combination with placebo on an animal model of sixteen New Zealand white rabbits. The intervention consisted of the instillation of one drop of a fixed combination containing 0.09 % xanthan gum and 0.1 % chondroitin sulfate on the right eye of each rabbit 6 times per day (every 2 h) in a 12-hour period for 15 days. The left eyes were used as control. Assessments on the anterior and posterior segment, ocular signs, and specific ocular surface characteristics were conducted at days 0, 1, 2, 4, 7, 10, and 15. Histopathological studies of the corneal and conjunctival epithelium were performed at the end of the intervention. No significant changes were observed during the assessments of the anterior and posterior segments. No differences in the number of goblet cells between groups were reported. The histopathological study of the corneal basement membrane's thickness, stromal, and conjunctival epithelium did not show significant changes between groups. The use of a fixed-dose combination containing 0.09 % xanthan gum and 0.1 % chondroitin sulfate on the ocular surface of New Zealand white rabbits every 2 h for 15 days causes no histopathological changes in anterior/posterior segments, nor a decrease in the number of goblet cells compared with placebo.

Effect of pantoprazole on insulin secretion in drug-naïve patients with type 2 diabetes.

To evaluate the effect of pantoprazole during 45 days on insulin secretion in drug-naïve patients with type 2 diabetes, a randomized, double blind, placebo control clinical trial was performed in 14 drug-naïve volunteers. Significant increases in late insulin phase and total insulin secretion, and decreases in HbA1c levels were found.

Effect of a combined continuous and intermittent transcutaneous electrical nerve stimulation on pain perception of burn patients evaluated by visual analog scale: a pilot study.

AIM: The aim of this study was to assess the effect of continuous and intermittent electrical transcutaneous nerve stimulation on the perception of pain in patients with burns of different types. MATERIALS AND METHODS: A pilot study was conducted in 14 patients (age 30.9±7.5 years) with second- and third-degree burns of different types. The burn types included electrical, fire/flame, and chemical. All patients received continuous and intermittent electrical transcutaneous nerve stimulation sessions three times per week for 4 weeks. Each session had a duration of 30 minutes. A pair of electrodes were placed around the burn. The primary efficacy endpoint was the perception of pain assessed by a visual analog scale at baseline and at the 30th day. RESULTS: A significant reduction of pain perception was reported (8.0±1.7 vs 1.0±0.5; P=0.027) by all patients after electrical stimulation therapy. There were no reports of adverse events during the intervention period. CONCLUSION: Electrical stimulation could be a potential nonpharmacological therapeutic option for pain management in burn patients.

Effect of avocado soybean unsaponifiables on insulin secretion and insulin sensitivity in patients with obesity.

AIM: To evaluate the effect of avocado soybean unsaponifiables (ASU) on insulin secretion and insulin sensitivity in patients with obesity. METHODS: A randomized, double-blind, placebo-controlled, clinical trial was carried out in 14 obese adult volunteers. After random allocation of the intervention, 7 patients received 300 mg of ASU or placebo during a fasting state for 3 months. A metabolic profile including IL-6 and high-sensitivity C-reactive protein (hs-CRP) levels was carried out prior to the intervention. A hyperglycemic-hyperinsulinemic clamp technique was used to assess insulin secretion and insulin sensitivity phases. Mann-Whitney U test and Wilcoxon test were performed for statistical analyses. The study was approved by the local ethics committee of our institution. RESULTS: At baseline, both groups were similar according to clinical and laboratory characteristics. There was no significant difference in insulin secretion and insulin sensitivity with ASU. CONCLUSIONS: ASU administration for 3 months did not modify insulin secretion and insulin sensitivity in patients with obesity.