Markers of Oxidative Stress in the Saliva of Type 2 Diabetic Patients

Objective: Diabetes mellitus is associated with increased prevalence of oral diseases for which reactive oxygen species have been implicated. The saliva contains protective antioxidants which statutorily curtail these destructive oxygen molecules. A functional compromise of the antioxidants may precipitate oxidative stress leading to the increased oral disease susceptibility. However, salivary markers of oxidative stress have not been sufficiently studied in the diabetics. Methods: A total of 166 adults were recruited for this study. They comprised of 95 Type 2 diabetic patients and 71 healthy non-diabetic controls. About 3 ml of unstimulated saliva samples were collected from participants and processed, levels of salivary H2O2, NO and MDA were measured using spectrophotometry method and compared between the two groups. Data was analysed using t-test, logistic regression and receiver operating characteristics (ROC) with statistical significance set at p<0.05. Results: Salivary H2O2 (p=0.024) and NO (p=0.002) were significantly higher in the diabetic patients when compared to the healthy non-diabetic control group. Binary logistic regression showed that patients with Type 2 diabetic mellitus are more likely to have elevated salivary H2O2 (OR= 1.013; p=0.025) and NO (OR=1.016; p=0.003) levels. ROC analysis showed statistically significant performance of salivary NO levels in distinguishing between T2DM patients and healthy controls. Conclusions: Higher levels of oxidative stress markers including salivary H2O2 and NO in the diabetic groups could be a pointer to the characteristic high prevalence of oral diseases in diabetes mellitus, given that oxidative stress predisposes to disease vulnerability. This calls for increased attention to oral health in diabetes management to minimise co-morbidity

A regimen containing bedaquiline and delamanid compared to bedaquiline in patients with drug-resistant tuberculosis.

There are limited data on combining delamanid and bedaquiline in drug-resistant tuberculosis (DR-TB) regimens. Prospective long-term outcome data, including in HIV-infected persons, are unavailable.We prospectively followed up 122 South African patients (52.5% HIV-infected) with DR-TB and poor prognostic features between 2014 and 2018. We examined outcomes and safety in those who received a bedaquiline-based regimen (n=82) compared to those who received a bedaquiline-delamanid combination regimen (n=40).There was no significant difference in 6-month culture conversion (92.5% versus 81.8%; p=0.26) and 18-month favourable outcome rate (63.4% versus 67.5%; p=0.66) in the bedaquiline versus the bedaquiline-delamanid combination group, despite the latter having more advanced drug resistance (3.7% versus 22.5% resistant to at least five drugs; p=0.001) and higher pre-treatment failure rates (12.2% versus 52.5% with pre-treatment multidrug-resistant TB therapy failure; p60 ms from baseline (p=0.001) or >450 ms during treatment (p=0.001)), there were no symptomatic cases or drug withdrawals in either group. Results were similar in HIV-infected patients.A bedaquiline-delamanid combination regimen showed comparable long-term safety compared to a bedaquiline-based regimen in patients with DR-TB, irrespective of HIV status. These data inform regimen selection in patients with DR-TB from TB-endemic settings

Linezolid interruption in patients with fluoroquinolone-resistant tuberculosis receiving a bedaquiline-based treatment regimen.

BACKGROUND: Treatment outcomes of patients with extensively drug-resistant tuberculosis (XDR-TB) are suboptimal and treatment options remain limited. Linezolid is associated with improved outcomes but also substantial toxicity, and details about the relationship between these are lacking from resource-poor HIV-endemic settings. METHODS: This was a prospective follow-up study of 63 South African XDR-TB patients (58.7% HIV-infected; median CD4 131 cells/μl) between 2014 and 2018. The frequency and severity of linezolid-associated adverse events and the impact on treatment outcomes were compared between linezolid interrupters and non-interrupters. RESULTS: Twenty-two patients (34.9%) discontinued or underwent dose reduction due to presumed linezolid-associated toxicity. Anaemia (77.3% vs. 7.3%; p< 0.001), peripheral neuropathy (63.6% vs. 14.6%; p= 0.003), and optic neuritis (18.2% vs. 9.8%; p= 0.34) occurred more frequently in linezolid interrupters than in non-interrupters. Anaemia, peripheral neuropathy, and optic neuritis occurred at a median of 5, 18, and 23 weeks, respectively, after treatment initiation. Linezolid interruption was not associated with unfavourable outcomes but was strongly associated with HIV co-infection (adjusted hazard ratio 4.831, 95% confidence interval 1.526-15.297; p= 0.007) and bacterial load (culture days to positivity; adjusted hazard ratio 0.824, 95% confidence interval 0.732- 0.927; p= 0.001). CONCLUSIONS: Linezolid-related treatment interruption is common, is strongly associated with HIV co-infection, and system-specific toxicity occurs within predictable time frames. These data inform the clinical management of patients with drug-resistant TB

Allele Frequencies of Apolipoprotein E in a South Western Nigerian population on HAART

Objective: Increasing evidence has shown that ApoE polymorphism is associated with the early onset of cardiovascular and neurological diseases in patients on HAART. The frequency of occurrence of the alleles and the genotypes vary by race and population. The study describes the pattern seen among adults in Ibadan, Nigeria. Methods: This cross-sectional study was conducted among 124 randomly selected HIV-infected persons on protease inhibitor therapy who receive care at the adult antiretroviral clinic of the University College Hospital (UCH), Ibadan. DNA was extracted from leucocytes using EDTA blood. ApoE genotypes were determined using the Seeplex ApoE ACE genotyping kit. The epidemiological distribution of apoE is figured with a pie graph. Results: About four-fifth (79%) of the participants were females while about two-thirds (68%) were below 50 years of age.&nbsp; The most frequently occurring allele was the ε3 allele (82.2%) and the most common ApoE genotype observed was ε3/ε3. This genotype was present in 52 (41.9%) of the participants. At least one allele of Apo ε2, Apo ε3, and Apo ε4 was present in 28(22.5%), 102 (82.2%), and 50 (40.3) of the study participants respectively. Homozygosity for Apo ε2 and Apo ε4 was observed in 4.8% and 8.0% of participants respectively. Conclusions: Allelic frequency seen is similar to that described in other studied populations and the frequency of genotypes observed was also similar to those described among world populations with a higher observation of ApoE4 allele as seen in people of African descent

Allele Frequencies of Apolipoprotein E in a South Western Nigerian population on HAART

Objective: Increasing evidence has shown that ApoE polymorphism is associated with the early onset of cardiovascular and neurological diseases in patients on HAART. The frequency of occurrence of the alleles and the genotypes vary by race and population. The study describes the pattern seen among adults in Ibadan, Nigeria. Methods: This cross-sectional study was conducted among 124 randomly selected HIV-infected persons on protease inhibitor therapy who receive care at the adult antiretroviral clinic of the University College Hospital (UCH), Ibadan. DNA was extracted from leucocytes using EDTA blood. ApoE genotypes were determined using the Seeplex ApoE ACE genotyping kit. The epidemiological distribution of apoE is figured with a pie graph. Results: About four-fifth (79%) of the participants were females while about two-thirds (68%) were below 50 years of age.  The most frequently occurring allele was the ε3 allele (82.2%) and the most common ApoE genotype observed was ε3/ε3. This genotype was present in 52 (41.9%) of the participants. At least one allele of Apo ε2, Apo ε3, and Apo ε4 was present in 28(22.5%), 102 (82.2%), and 50 (40.3) of the study participants respectively. Homozygosity for Apo ε2 and Apo ε4 was observed in 4.8% and 8.0% of participants respectively. Conclusions: Allelic frequency seen is similar to that described in other studied populations and the frequency of genotypes observed was also similar to those described among world populations with a higher observation of ApoE4 allele as seen in people of African descent

Examining Rational Bubbles in Oil Prices: Evidence From Frequency Domain Estimates

This study examined the existence of rational bubbles in oil prices by employing a frequency domain econophysics technique that have capacity to identify both explosive behaviour and bubbles in oil prices for the three largest oil future markets – WTI, Brent and OPEC basket. Our results show that the three prices experienced bubbles in four distinct periods. We attempt to provide some explanations on each of these bubbles using geopolitical, war and economic events. We equally noted that oil prices bubbles are largely influenced by the fact that oil is a major source of energy and is non-renewable. The study observed that existence of bubbles have some economic consequences such as welfare loss resulting from distortion in prices and economic instability among others. We provide some policy recommendation. Keywords: oil prices, rational bubbles, energy JEL Classifications: C22, C50, G10, G12 DOI: https://doi.org/10.32479/ijeep.746

Efficacy and safety of novel and repurposed drugs for the treatment of drug-resistant tuberculosis

Background: There is widespread concern about the rise of drug-resistant TB because treatment outcomes of affected patients remain poor and treatment options are limited. After more than a forty-year gap without any breakthrough discovery, several new (bedaquiline and delamanid) and repurposed drugs (linezolid) are increasingly becoming available for use. However, data regarding the efficacy and safety of these drugs in drug-resistant TB patients, with or without HIV infection, from a real-life programmatic setting are lacking. This thesis aims to address that knowledge gap and provide information for management of drug-resistant TB in countries with high disease burden. Methods: A total of 326 drug resistant TB patients were prospectively followed up between January 2008 and April 2018. The efficacy and safety of two new drugs (bedaquiline and delamanid) and one repurposed drug (linezolid) was determined in these patients in three studies. In the first study, 24 months treatment outcomes and adverse event profiles were compared between extensively drug resistant (XDR) TB patients who received programmatic treatment regimens with the backbone of second line injectables and fluoroquinolones (nonbedaquiline-based) and those who received a bedaquiline- and/ or linezolid-based treatment regimen. The second study determined the frequency of system-specific adverse events associated with linezolid. The third study interrogated the safety and effectiveness of a strengthened treatment regimen containing a combination of delamanid and bedaquiline in patients with poor prognostic features compared to bedaquiline-based regimen. Results: In the first study, patients who received a bedaquiline-based treatment regimen had a significantly greater favourable outcome rate (66.2% vs 13.2%; p<0.001) ), more than a fourfold reduction in treatment failure rate (5.9% vs 26%; p<0.001 ) and less than a half of mortality rate compared to patients who received a non-bedaquiline-based regimen. The bedaquiline survival and favourable outcome effect remained significant in HIV-infected patients (p<0.001). The second study showed that linezolid interruption was common in patients receiving a bedaquiline-based treatment regimen, and that system-specific toxicity occurred within predictable time frames. It also showed that anaemia (77.3% versus 7.3%; p<0.001), peripheral neuropathy (63.6% versus 14.6%; p=0.003), and optic neuritis (18.2% versus 9.8%; p=0.34) occurred more frequently in linezolid interrupters than in non-interrupters. The third study showed that the use of delamanid-bedaquiline combination regimen was safe and efficacious in drug resistant TB patients with poor prognosis when compared with outcomes in the less sick patients who received a bedaquiline-based regimen. It also showed no significant difference in culture conversion rate at 6 months (92.5% versus 81.8%; p=0.26) or favourable treatment outcome rate (63.4% versus 67.5%; p=0.66) between the two groups. Although patients who received the combination regimen had more frequent occurrence of QTcF prolongation greater than 60 ms from baseline (p=0.001) and more episodes of QTcF greater than 450 ms during treatment (p=0.001), none of them were symptomatic or had delamanid or bedaquiline withdrawn from their regimen. Conclusion: These data demonstrated that new and repurposed drugs remarkably improved treatment outcomes in patients with drug-resistant TB. Although linezolid, which is an important component of the bedaquiline-based treatment regimen, is often associated with system-specific adverse events, these occurred at predictable time frames thereby guiding physicians to make informed management decisions. Lastly, drug resistant TB patients with poor prognosis may benefit from a regimen containing delamanid and bedaquiline which seems relatively safe from an adverse event perspective. These data, despite some limitations, make a case for a widespread and accelerated roll-out of new and repurposed drugs for the treatment of drug resistant TB

Salivary immunoglobulin classes in Nigerian cigarette smokers: Indication for increased risk of oral diseases

Background: Cigarette smoking is a worldwide social epidemic and it is one of the main causes of preventable death and disability. Gingivitis, periodontitis, pocket depth, attachment loss, alveolar bone loss, and tooth loss are some of oral pathologies commonly found in cigarette smokers. The aim of this study was to explore, for the first time among Nigerians, the interplay between components of cigarette smoke and salivary levels of immunoglobulin classes so as to provide oral immunological based reasons for oral diseases in cigarette smokers. Materials and Methods: In this case-control study, 5 mL of unstimulated saliva was collected in plain sample bottles from 24 active smokers who smoke at least 6 sticks of cigarette per day and 21 sex and age-matched non-smokers who were apparently healthy. The samples were spun and supernatant stored at -20°C until assayed. The immunoglobulin levels of the samples were estimated using enzyme-linked immunosorbent assay (ELISA). Student′s t-test (unpaired) was used to determine significant differences between the two groups. P values less than 0.05 was considered significant. Results: No significant differences were observed in the mean salivary levels of IgG, IgA, and IgE. Only IgM was significantly lower in smokers compared with non-smokers (P = 0.038). The proportion of smokers with detectable level of salivary IgE was lower compared with controls. Conclusion: Our study showed that there is decreased salivary IgM in smokers. This observation suggests that reduced salivary immunoglobulin level of IgM might be involved in the pathogenesis of oral diseases in cigarette smokers

Levels of Salivary Immunoglobulin A and Immunoglobulin G in Type 2 Diabetic Patients

Background: Diabetes mellitus is a chronic disorder of glucose metabolism and it is associated with a compromised oral immunity. Salivary immunoglobulins offer a comprehensive protection for the oral cavity; however, there is insufficient data regarding their levels in type 2 diabetic patients. This study aimed to measure salivary Immunoglobulin G (IgG) and Immunoglobulin A (IgA) in diabetic patients in comparison to healthy nondiabetic controls. Methods: Diabetic patients from the outpatient clinic and nondiabetic healthy members of staff, were recruited for this study. Unstimulated saliva samples were collected from all participants and levels of immunoglobulins A and G were determined using enzyme-linked immunosorbent assay techniques; the values were compared between the two groups. Results: A total of 167 participants were recruited for this study, 95 (56.9%) of them were diabetic patients, while the remaining 72 (43.1%) were healthy nondiabetic controls. The median salivary IgA was 12.57 (Interquartile range [IQR] 11.05–13.67) g/ml in the diabetics and 11.94 (IQR 10.41–13.65) µg/ml in the control group; P = 0.31 while the median salivary IgG was 32.27 (IQR 25.26–38.33) µg/ml in the diabetics and 26.26 (22.48–31.29) µg/ml in the control group; P &lt; 0.001. Conclusion: Salivary IgG was significantly elevated in the diabetic patients, in spite of a higher prevalence of oral infections, this calls for a more stringent attention to oral hygiene in diabetic patients