The Potential Use of Orange and Banana Peels to Minimize the Toxicological Effects of Silver Nanoparticles in Oreochromis Niloticus

Bulletin of Environmental Contamination and Toxicology - To evaluate the effectiveness of orange peels (OP) and banana peels (BP) in reducing the toxicity of silver nanoparticles (Ag-NPs),...     

Methimazole in the Treatment of Melasma: A Clinical and Dermascopic Study

BACKGROUND: Melasma is a chronic hypermelanotic disorder that is challenging to treat; no single effective therapeutic agent for it has been discovered. Methimazole, an oral antithyroid drug, has a skin depigmenting effect when used topically. OBJECTIVE: We sought to evaluate the efficacy and safety of methimazole, applied during microneedling sessions and additional topical use in between sessions, for the treatment of melasma. METHODS: This split-face study included 30 Egyptian patients with melasma, each of whom received 12 microneedling sessions once per week for 12 weeks followed by topical methimazole on the right side of face and placebo on the left side. In between the sessions, topical methimazole 5% cream was applied twice per day on the right side and placebo on the left side. Assessments were performed using the Hemi-melasma Area and Severity Index (hemi-MASI) percentage of improvement, patient satisfaction, dermoscopy, and thyroid-stimulating hormone (TSH) serum levels. RESULTS: There were significant clinical and dermoscopic improvements; hemi-MASI scores on the methimazole-treated right sides were decreased (p<0.001). The percent of hemi-MASI score improvement was significantly associated with the malar pattern (p=0.031) and epidermal type (p=0.04) of melasma. About 70 percent of our studied patients reported being satisfied with their treatment response (7% excellent, 33% good, 30% fair). No significant local or systemic side effects were observed. Pre- and posttreatment serum TSH levels were within the normal range in all treated cases. CONCLUSIONS: Methimazole has the potential to be a safe and promising therapeutic agent for the treatment of melasma via dermapen-delivered microneedling sessions with topical use in between sessions.     

Bile acid indices as biomarkers for liver diseases I: Diagnostic markers

BACKGROUNDHepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis.AIMTo discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA profile.METHODSWe analyzed urine samples by liquid chromatography-tandem mass spectrometry and compared the urinary BA profile between 300 patients with hepatobiliary diseases vs 103 healthy controls by statistical analysis. The BA profile was characterized using BA indices, which quantifies the composition, metabolism, hydrophilicity, and toxicity of the BA profile. BA indices have much lower inter- and intra-individual variability compared to absolute concentrations of BA. In addition, BA indices demonstrate high area under the receiver operating characteristic curves, and changes of BA indices are associated with the risk of having a liver disease, which demonstrates their use as diagnostic biomarkers for cholestatic liver diseases.RESULTSTotal and individual BA concentrations were higher in all patients. The percentage of secondary BA (lithocholic acid and deoxycholic acid) was significantly lower, while the percentage of primary BA (chenodeoxycholic acid, cholic acid, and hyocholic acid) was markedly higher in patients compared to controls. In addition, the percentage of taurine-amidation was higher in patients than controls. The increase in the non-12α-OH BA was more profound than 12α-OH BA (cholic acid and deoxycholic acid) causing a decrease in the 12α-OH/ non-12α-OH ratio in patients. This trend was stronger in patients with more advanced liver diseases as reflected by the model for end-stage liver disease score and the presence of hepatic decompensation. The percentage of sulfation was also higher in patients with more severe forms of liver diseases.CONCLUSIONBA indices have much lower inter- and intra-individual variability compared to absolute BA concentrations and changes of BA indices are associated with the risk of developing liver diseases.     

Ischemic Pressure vs Postisometric Relaxation for Treatment of Rhomboid Latent Myofascial Trigger Points: A Randomized,Blinded Clinical Trial

ObjectiveThe purpose of this study was to investigate the effects of ischemic pressure (IP) vs postisometric relaxation (PIR) on rhomboid-muscle latent trigger points (LTrPs).MethodsForty-five participants with rhomboid-muscle LTrPs were randomly assigned into 3 groups and received 3 weeks of treatment—group A: IP and traditional treatment (infrared radiation, ultrasonic therapy, and transcutaneous electrical nerve stimulation); group B: PIR and traditional treatment; and group C: traditional treatment. Shoulder pain and disability, neck pain and disability, and pressure pain threshold (PPT) of 3 points on each side were measured before and after treatment.ResultsMultivariate analysis of variance indicated a statistically significant Group × Time interaction (P = .005). The PPT for the right lower point was increased in group A more than in groups B or C. Neck pain was reduced in group B more than in group C. Moreover, shoulder and neck disability were reduced in both groups A and B more than in group C. The PPTs of the left lower and middle points were increased in group B compared with groups A and C. The PPT of the left upper point was increased in group A more than in group C. There were significant changes in all outcomes in the 2 experimental groups (P < .05). No changes were found in the control group except in pain intensity, shoulder disability, and PPT of the left lower point.ConclusionThis study found that IP may be more effective than PIR regarding PPT, but both techniques showed changes in the treatment of rhomboid-muscle LTrPs.     

Birth prevalence of non-syndromic orofacial clefts in Saudi Arabia and the effects of parental consanguinity

Objectives:

To describe the characteristics and prevalence of non-syndromic orofacial clefting (NSOFC) and assess the effects of parental consanguinity on NSOFC phenotypes in the 3 main cities of Saudi Arabia.

Methods:

All infants (114,035) born at 3 referral centers in Riyadh, and 6 hospitals in Jeddah and Madinah between January 2010 and December 2011 were screened. The NSOFC cases (n=133) were identified and data was collected through clinical examination and records, and information on consanguinity through parent interviews. The diagnosis was confirmed by reviewing medical records and contacting the infants’ pediatricians. Control infants (n=233) matched for gender and born in the same hospitals during the same period, were selected.

Results:

The prevalence of NSOFC was 1.07/1000 births in Riyadh, and 1.17/1000 births overall; cleft lip (CL) was 0.47/1000 births, cleft lip and palate (CLP) was 0.42/1000 births, and cleft palate (CP) was 0.28/1000 births. Cleft palate was significantly associated with consanguinity (p=0.047, odds ratio: 2.5, 95% confidence interval: 1 to 6.46), particularly for first cousin marriages.

Conclusion:

The birth prevalence of NSOFC in Riyadh alone, and in the 3 main cities of Saudi Arabia were marginally lower than the mean global prevalence. While birth prevalence for CLP was comparable to global figures, the CL:CLP ratio was high, and only CP was significantly associated with consanguinity.Non-syndromic orofacial clefting (NSOFC), including isolated cleft lip (CL), cleft lip and palate (CLP), and isolated cleft palate (CP), is the most common craniofacial defect worldwide with an estimated mean global prevalence of 1.25/1000 live births.1 However, the prevalence of NSOFC varies geographically and across different ethnic groups.2 Although the ethnicity of the Middle East is considered Caucasian,3,4 geographically it is located between 3 continents (Asia, Africa, and Europe), which makes it unique and, in reality, a mixture of 3 ethnicities. A small number of studies have measured the prevalence of NSOFC in Saudi Arabia and neighboring countries with the reported prevalence ranging from 0.3 to 2.19/1000 births,5-9 and a mean value for all studies of 1.25/1000 births.10 In addition, consanguineous relationships have been suggested to increase the prevalence of congenital anomalies.11 These were also reported to be associated with NSOFC in a meta-analysis carried out on 16 studies that assessed the relationship between NSOFC and paternal consanguinity.12 Saudi Arabia, one of the largest countries in the Middle East, has a high rate of consanguineous marriage that varies between regions.13 Riyadh, which is the capital city of Saudi Arabia with a population of approximately 7.5 million and birth prevalence of 38,000/year,14,15 has a consanguinity marriages prevalence of 60%.16 The aims of this study were to 1) describe the characteristics and prevalence of NSOFC (CL, CLP, and CP) in Riyadh (the capital city in the central region of Saudi Arabia), 2) describe the prevalence of NSOFC phenotypes, and 3) the relationship between these and consanguinity in Saudi Arabia.     

Closure of large oroantronasal fistula residual after gunshot injuries with temporalis muscle flap

Large oroantronasal fistulas have a detrimental effect on patient nutrition and speech, not to mention its moral effect when combined with devastating deformity associated with high-energy gunshot injuries to the face. Despite the fact that temporalis muscle flap was first described nearly 116 years ago, it still represents a useful tool in craniofacial and oral reconstruction. The aim of this article was to describe the utilization of temporalis muscle flap for reconstructing large oroantronasal fistula residual after gunshot injuries. Three clinical cases were described with emphasis on surgical technique. The flap was reliable because of its rich blood supply and close proximity to the oral cavity. Major complications were not observed. In hospitals lacking facilities for extensive reconstructive procedure, temporalis muscle flap should be taken into consideration when tackling difficult oral defects.     

Species differences in bile acids II. Bile acid metabolism

One of the mechanisms of drug‐induced liver injury (DILI) involves alterations in bile acid (BA) homeostasis and elimination, which encompass several metabolic pathways including hydroxylation, amidation, sulfation, glucuronidation and glutathione conjugation. Species differences in BA metabolism may play a major role in the failure of currently used in vitro and in vivo models to predict reliably the DILI during the early stages of drug discovery and development. We developed an in vitro cofactor‐fortified liver S9 fraction model to compare the metabolic profiles of the four major BAs (cholic acid, chenodeoxycholic acid, lithocholic acid and ursodeoxycholic acid) between humans and several animal species. High‐ and low‐resolution liquid chromatography–tandem mass spectrometry and nuclear magnetic resonance imaging were used for the qualitative and quantitative analysis of BAs and their metabolites. Major species differences were found in the metabolism of BAs. Sulfation into 3‐O‐sulfates was a major pathway in human and chimpanzee (4.8%–52%) and it was a minor pathway in all other species (0.02%–14%). Amidation was primarily with glycine (62%–95%) in minipig and rabbit and it was primarily with taurine (43%–81%) in human, chimpanzee, dog, hamster, rat and mice. Hydroxylation was highest (13%–80%) in rat and mice followed by hamster, while it was lowest (1.6%–22%) in human, chimpanzee and minipig. C6‐β hydroxylation was predominant (65%–95%) in rat and mice, while it was at C6‐α position in minipig (36%–97%). Glucuronidation was highest in dog (10%–56%), while it was a minor pathway in all other species (<12%). The relative contribution of the various pathways involved in BA metabolism in vitro were in agreement with the observed plasma and urinary BA profiles in vivo and were able to predict and quantify the species differences in BA metabolism. In general, overall, BA metabolism in chimpanzee is most similar to human, while BA metabolism in rats and mice is most dissimilar from human.     

Enhanced bioavailability of buspirone hydrochloride via cup and core buccal tablets: Formulation and in vitro/in vivo evaluation

This work aims to prepare sustained release buccal mucoadhesive tablets of buspirone hydrochloride (BH) to improve its systemic bioavailability. The tablets were prepared according to 5 × 3 factorial design where polymer type was set at five levels (carbopol, hydroxypropyl methylcellulose, sodium alginate, sodium carboxymethyl cellulose and guar gum), and polymer to drug ratio at three levels (1:1, 2:1 and 3:1). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h) and time for release of 50% BH (T_50%) were chosen as dependent variables. Additional BH cup and core buccal tablets were prepared to optimize BH release profile and make it uni-directional along with the tablets mucoadhesion. Tablets were evaluated in terms of content uniformity, weight variation, thickness, diameter, hardness, friability, swelling index, surface pH, mucoadhesion strength and time and in vitro release. Cup and core formula (CA10) was able to adhere to the buccal mucosa for 8 h, showed the highest Q8h (97.91%) and exhibited a zero order drug release profile. Pharmacokinetic study of formula CA10 in human volunteers revealed a 5.6 fold increase in BH bioavailability compared to the oral commercial Buspar^® tablets. Conducting level A in vitro/in vivo correlation showed good correlation (r² = 0.9805) between fractions dissolved in vitro and fractions absorbed in vivo.