Effectiveness and Safety of Topical Under-eye Serum in Patients with Periorbital Hyperpigmentation: An Open-label Single Arm Prospective Study

ObjectiveWe sought to determine the efficacy and safety of a topical under-eye serum (Melalumin™; Menarini India Pvt Ltd.) in patients with periorbital hyperpigmentation (POH).MethodsIn this prospective, open-label single-arm study, 90 patients aged 18 to 55 years with Grade I to IV pigmentary POH, were given the under-eye serum for three months. Follow-up visits were scheduled at one, two and three months from baseline. Effectiveness was evaluated by two independent dermatologists using a skin colorimeter (Dermacatch) and dermoscopy (FotoFinder Systems, Inc., Medical Imaging Systems; Columbia, Maryland), as well as global photographs and patient-reported satisfaction ratings (excellent, very good, good, not satisfied). Adverse events were recorded. The colorimeter values were evaluated using the paired T test and the single-mean T test was used for dermoscopy and global clinical photographs.ResultsOf the 90 patients included, 85 completed the study. Significant reductions in colorimeter values were noted in both melanin (from 708 to 621) and erythema (from 450 to 417) over three months (p<0.05). Mean improvement in dermoscopic assessment was 48.41 percent; Most (n=73/85; 85.88%) patients achieved >25-percent improvement; over one-third (n=31/85; 36.47%) showed >50-percent improvement. Global photographs improved by 49.47 percent; most (n=75/85; 88.24%) patients showed >25-percent improvement, over one-third (n=38/85; 44.71%) showed >50-percent improvement. Patient satisfaction levels were high (Excellent: 16 [18.82%]; Very good: 38 [44.71%]); Good: 26 [30.59%]; Not satisfied: 5 [5.88%]). No adverse events were noted.ConclusionThis study demonstrates safety and effectiveness of the studied under-eye serum in patients with pigmentary POH. In addition to clinical improvements noted by the investigators, significant improvements were also noted in colorimeter values, dermoscopy results, and global photographs. Patients exhibited high satisfaction levels with treatment outcomes. No safety concerns were noted.     

Collateral damage: Corneal injury due to mask use during the COVID-19 pandemic - A case series

Though masks are the best shield against COVID-19, they can be a source of discomfort and ocular side effects. We discuss three cases of corneal injury due to mask use. Three patients, who were healthcare workers, presented with discomfort, photophobia, and pain in the eyes. While adjusting the mask, they had an ocular injury. There were multiple superficial linear abrasions in the eyes. They recovered with treatment. Though masks are imperative during the COVID-19 pandemic, it is important to be aware of a possible mask injury.     

Efficacy of 'Gamadent' toothpaste on the healing of gingival tissues: a preliminary report

The aim of this randomised, parallel, double-blind study, in which 28 adult patients diagnosed with chronic gingivitis or early stages of chronic periodontitis were recruited, was to evaluate the efficacy of 'Gamadent' toothpaste compared to a placebo toothpaste. 'Gamadent' toothpaste has all the basic constituents of a toothpaste with the addition of a sea cucumber extract (SCE) of the species Stichopus sp. 1 to improve the healing potential of tissues. The placebo has the same basic constituents minus the extract. Out of the 28 patients, 14 were placed in the test group who used the 'Gamadent' toothpaste, and 14 patients were placed in the control group (2 control subjects defaulted and were excluded), who brushed using the placebo toothpaste. The longitudinal study was carried out over a period of 3 months with assessments made at baseline, 1 month, 2 months and 3 months after conventional therapy at the baseline visit. The clinical parameters used during the trial were Plaque Index (PI), Gingival Index (GI), Papilla Bleeding Index (PBI) and Probing Pocket Depth (PPD). A predetermined number of sites on a molar, premolar, canine and an incisor were examined and evaluated in each quadrant. After the baseline assessment, the patients had full mouth scaling and debridement as well as oral hygiene instructions. Patients were instructed to brush their teeth twice a day with the toothbrush provided (Oral-B plus, size 35) and toothpaste (test or control), using the Bass technique. At the 1-month assessment, there were significant mean reductions to baseline mean values in PI (P < 0.005) and GI (P < 0.001) in the test group as compared to the control group. At the end of the 2-month interval, significant reductions were observed in PI, PBI and PPD (P < 0.001). By the end of 3 months, there were significant differences in the mean reduction of all the parameters i.e. PI, PBI, GI and PPD (P < 0.001), between the test and control sites. In conclusion, 'Gamadent' toothpaste provided noteworthy benefits, producing statistically significant improvement in all clinical parameters compared to the placebo during the healing phase after conventional initial therapy.     

Glycosylated hemoglobin-defined prediabetes and cardiovascular risk markers in rural India: the Nallampatti noncommunicable disease study

The aim of this study is to assess the associations between glycosylated hemoglobin in the prediabetes range and cardiovascular risk markers in a rural South Indian population. Local Ethics Committee approval and informed consent was obtained from all participants. Inclusion criteria were participants, aged ≥20 and ≤85 years, from Nallampatti, a classical farming village from Tamil Nadu State, India. Those with known history of diabetes were excluded from this analysis. All participants were administered a detailed questionnaire, had anthropometric measurements including height, weight, and waist circumference. Bloods were drawn for random blood glucose, glycosylated hemoglobin, nonfasting lipid profile, cystatin C, uric acid, and hemoglobin. All participants had carotid intima thickness done by high-resolution B-mode carotid ultrasound. Progressive hyperglycemia across the glucose tolerance continuum based on glycosylated hemoglobin levels in a rural South Indian population seems to be associated with worsening cardiovascular risk markers. A cut-off value of ≥6% (42 mmol/mol) seems to herald a much more significant increase in such markers. Long-term follow-up of this cohort for incident cardiovascular disease will help to substantiate the associations between glycosylated hemoglobin levels within the prediabetes range and cardiovascular disease in an Indian population. Evidence-based race-specific criteria for diagnosis of prediabetes and diabetes are the need of the hour for risk stratification and appropriate management.     

Rapid pulsed-field gel electrophoresis protocol for subtyping of Campylobacter jejuni

We developed a rapid pulsed-field gel electrophoresis (PFGE) protocol for subtyping Campylobacter isolates based on the standardized protocols used by PulseNet laboratories for the subtyping of other food-borne bacterial pathogens. Various combinations of buffers, reagents, reaction conditions (e.g., cell suspension concentration, lysis time, lysis temperature, and restriction enzyme concentration), and electrophoretic parameters were evaluated in an effort to devise a protocol that is simple, rapid, and robust. PFGE analysis of Campylobacter isolates can be completed in 24 to 30 h using this protocol, whereas the most widely used current protocols require 3 to 4 days to complete. Comparison of PFGE patterns obtained in six laboratories showed that subtyping results obtained using this protocol are highly reproducible.     

Progressive fetal atrioventricular block in heterotaxy syndrome

We report a fetus with left isomerism, in whom the atrioventricular block progressed from low grade second degree to complete block and fetal hydrops. While it is known that there is a high incidence of heart block in the fetus with left isomerism, as far as we are aware, ours is the first report of Wenckebach type block documented in the fetus by Doppler echocardiography, and demonstration of the progression of heart block during fetus life in the setting of left isomerism.     

Changes in serum vitamin B12 levels in patients with megaloblastic anaemia treated with folic acid

In 21 patients with megaloblastic anaemia associated with the tropical malabsorption syndrome serum vitamin B₁₂ levels have been measured serially before and during parenteral folic acid therapy.     

AMP-kinase alpha2 subunit gene PRKAA2 variants are associated with total cholesterol, low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol in normal women

Background

5′‐AMP‐activated protein kinase (AMPK) inactivates critial ensymes in fatty acid and cholesterol synthesis. We hypothesised that the serum lipid profile may be influenced by genetic variation in the AMPK catalytic α2 subunit.

Method

We examined association of 5 tagging SNPs (tSNPs) in the PRKAA2 gene with serum lipids in 2777 normal Caucasian females (mean age 47.4±12.5 years).

Results

All tSNPs were associated with total‐ and LDL‐cholesterol, (p<0.001 to 0.034), explaining variances of 0.13–0.59% and 0.11–0.55% respectively. One haplotype (frequency 34.7%) showed lower total‐ and LDL‐cholesterol compared with the most common haplotype (frequency 45.7%) (p≤0.001), explaining 0.78% of total‐ and 0.75% of LDL‐cholesterol. Another haplotype (frequency 10.5%) was significantly associated with lower HDL‐cholesterol (p = 0.005), explaining 0.59% of variance.

Conclusions

PRKAA2 gene variants are significantly associated with serum lipoproteins in a large sample of normal female Caucasians.Known as the “fuel gauge of the cell”,¹ 5′‐AMP‐activated protein kinase (AMPK), is activated by an increase in the cellular AMP:ATP ratio after ATP depletion. Once activated, AMPK switches on ATP‐generating (catabolic) pathways and switches off ATP‐consuming (anabolic) pathways, allowing the cell to restore its energy balance.² In addition to its response to acute changes in energy levels in individual cells, AMPK also plays an important part in the regulation of whole‐body energy metabolism (see Kahn et al³ for review). For example, in the liver, AMPK phosphorylates and inactivates both acetyl‐coenzyme A carboxylase and 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A (HMG‐CoA) reductase.⁴ Acetyl‐coenzyme A carboxylase catalyses the biosynthesis of malonyl‐CoA, which is the initial substrate for fatty acid synthesis and an inhibitor of carnitine palmitoyl transferase‐1, the rate‐limiting step for mitochondrial fatty acid oxidation.⁵ HMG‐CoA reductase is the rate‐limiting enzyme of cholesterol synthesis.⁶ AMPK activity therefore inhibits fatty acid and cholesterol biosynthesis and promotes fatty acid oxidation, thereby opposing intracellular lipid accumulation and development of insulin resistance in non‐adipose tissues.

Key points

• Association study of five tagging single‐nucleotide polymorphisms (tSNPs) in the 5′‐AMP‐activated protein kinase α2 subunit gene PRKAA2 in 2777 normal Caucasian women (mean (SD) age 47.4 (12.5) years).
• All tSNPs were significantly associated with total cholesterol and low‐density lipoprotein (LDL)‐cholesterol (p<0.001 to 0.034).
• One haplotype was associated with lower total cholesterol and LDL‐cholesterol (all p⩽0.001) and another with lower high‐density lipoprotein‐cholesterol (p = 0.005), compared with the common haplotype.

AMPK is a heterotrimeric complex comprising a catalytic subunit (α) and two regulatory subunits (β and γ). In humans, there are isoforms of all three subunits, encoded by separate genes. Compared with the wild type, AMPK α2‐knockout mice exhibit increased body weight and fat mass when exposed to a high‐fat diet,⁷ and have impaired insulin sensitivity.⁸ Expression of a constitutively active mutant AMPK α subunit in insulin‐resistant human HepG2 cells has been shown to decrease intracellular triglyceride and cholesterol.⁹We hypothesised that regulation of the lipid profile, affecting body fat deposition and sensitivity of target organs to insulin, may be potentially mediated by differential expression or activity of the AMPK α2 subunit. No population studies have examined variations in the AMPK α2 subunit gene PRKAA2 with respect to serum lipids or measures of body fat. In a recent study, Sun et al¹⁰ found no association between PRKAA2 tagging single‐nucleotide polymorphisms (tSNPs) and type 2 diabetes in five independent Caucasian samples, nor with serum glucose and insulin in normal subjects. In another recent study, Horikoshi et al¹¹ found no independent associations between PRKAA2 single‐nucleotide polymorphisms (SNPs) and type 2 diabetes in Japanese subjects, but found one associated haplotype, which was replicated in three case–control groups. Neither study measured serum lipids. Recently, Xu et al¹² found that rare homozygotes of an intronic SNP in the regulatory AMPK γ2 subunit gene PRKAG2 had significantly higher serum concentrations of triglycerides and total cholesterol than common allele carriers (n = 290; p = 0.01). In Chinese people, therefore, it seems that AMPK γ2 polymorphisms might be associated with lipid metabolism. The γ2 isoform has broad tissue distribution, but the only known functional mutations interfere with AMP activation of AMPK and cause hypertrophic cardiomyopathy associated with Wolff–Parkinson–White syndrome.¹³We have used a multistep design in a large study sample to examine association of PRKAA2 variants with adiposity and lipid phenotypes, on a gene‐wide level.¹⁴ tSNPs effectively capture information of all common variants by taking into account patterns of linkage disequilibrium across the gene.^15,16 We tested their effect, individually and as haplotypes, on a range of variables, including anthropometry, serum lipids and body fat distribution, in a sample of Caucasian female twins (n = 2771, mean (SD) age 47.4 (12.5) years) and established strong associations across the gene with serum low‐density lipoprotein (LDL)‐cholesterol and total cholesterol levels. We have attempted a fine mapping analysis using the tSNPs to predict potential associations between the remaining (ungenotyped) SNPs and serum cholesterol to suggest potential functional sites.¹⁵