Takayasu’s arteritis occurring under TNF blockers in a patient with spondyloarthritis: is it an association or a paradoxical effect?

Coexistence of spondyloarthritis (SpA) and Takayasu’s arteritis is not a common finding, but such cases have been discussed, particularly in the context of choice of therapy. Inhibition of inflammation by tumor necrosis factor inhibitors (TNFi) is a key aspect of the treatment of SpA and also positive effects of such treatment in concomitant large vessel vasculitis have been reported. However, TNFi is also associated with the possibility of initiating vasculitis.The present article based on a case study and the available literature is an attempt to discuss coexistence of these two diseases and the impact of treatment with biological drugs from the anti-TNF group in the course of SpA with Takayasu’s arteritis.     

A randomized,double-blind placebo-controlled add-on trial to assess the efficacy,safety, and anti-atherogenic effect of spirulina platensis in patients with inadequately controlled type 2 diabetes mellitus

The efficacy of spirulina platensis (S. platensis) as an add-on therapy to metformin and its effect on atherogenic keys in patients with uncontrolled Type 2 Diabetes Mellitus (T2DM) was evaluated. Sixty patients were randomly assigned to S. platensis (2 g/day) or placebo group for three months while continuing metformin as their usual treatment. The efficacy of S. platensis was determined using the pre- and post-intervention HbA1c levels (primary outcome) as well as tracking FBS and lipid profiles levels (TC, LDL-C, TG, and HDL-C) as secondary outcomes at the different treatment time points (0,30,60,90 days). During the three–month intervention period, supplementation with S. platensis resulted in a significant lowering of HbA1c (↓1.43, p < 0.001) and FBS (↓ 24.94 mg/dL, p < 001) levels. Mean TG in the intervention group was found to be significantly lower in the intervention group than in controls (p < 0.001). Total cholesterol (TC) and its fraction, LDL-C, exhibited a fall (↓41.36 mg/dL and ↓38.4 mg/dL, respectively; p < 0.001) coupled with a marginal increase in the level of HDL-C (↑3 mg/dL; p < 0.001). Add-on therapy with S. platensis was superior to metformin regarding long-term glucose regulation and controlling blood glucose levels of subjects with T2DM. Also, as a functional supplement, S. platensis has a beneficial effect on atherogenic keys (TG and HDL-C) with no adverse events.     

Physical activity combined with massage improves bone mineralization in premature infants: a randomized trial.

BACKGROUND: Osteopenia of prematurity is a known source for morbidity in preterm infants. Premature infants have shown favorable outcomes in response to massage and physical activity. Whether such intervention can stimulate bone formation or decrease bone resorption is yet to be determined. OBJECTIVE: To test the hypothesis that massage combined with physical activity can stimulate bone formation and ameliorate bone resorption in premature infants. DESIGN/METHODS: A prospective double-blinded randomized trial was conducted at the Neonatal Intensive Care Unit of Ain Shams University in Cairo, Egypt. Thirty preterm infants (28 to 35 weeks' gestation) were randomly assigned to either control group (Group I, n=15) or intervention group (Group II, n=15). Infants in the intervention group received a daily protocol of combined massage and physical activity. Serum type I collagen C-terminal propeptide (PICP) and urinary pyridinoline crosslinks of collagen (Pyd) were used as indices for bone formation and resorption, respectively. PICP and Pyd were measured at enrollment and at discharge for all subjects. t-Test, ANOVA and linear regression analysis were used for statistical analyses. RESULTS: There was no difference between groups I and II in gestational age (32.1+/-1.8 vs 31.5+/-1.4 weeks) or birth weight (1.429+/-0.148 vs 1.467+/-0.132 g). In the control group, serum PICP decreased over time from 82.3+/-8.5 to 68.78+/-14.6 (p<0.01), while urinary Pyd increased from 447.7+/-282.8 to 744.9+/-373.6 (p<0.01) indicating decreased bone formation and increased bone resorption, respectively. In the intervention group, serum PICP increased over time from 62.5+/-13.8 to 73.84+/-12.9 (p<0.01). Urinary Pyd also increased over time from 445.7+/-266.5 to 716.8+/-301.8 (p<0.01). In a linear regression model including gestational age and intervention, serum PICP increased significantly in the intervention group (regression coefficient 18.8+/-4.6, p=0.0001) while urinary Pyd did not differ between groups (regression coefficient=5.6+/-114.3, p=0.961). CONCLUSIONS: A combined massage and physical activity protocol improved bone formation (PICP) but did not affect bone resorption (Pyd). Pyd increased over time in both groups, possibly due to continuous bone resorption and Ca mobilization.     

A novel protocol for postpartum magnesium sulphate in severe pre-eclampsia: a randomized controlled pilot trial

Objective: Magnesium sulphate is the preferred anticonvulsant used to prevent the development of fits in severe pre-eclampsia; we aim to compare between three different protocols of postpartum magnesium sulphate in the effectiveness of preventing the development of fits in severe pre-eclampsia.

Methods: Double-blind randomized controlled pilot trial, done in Cairo university hospital, Cairo, Egypt during 2013–2014, on 240 women with severe pre-eclampsia. Magnesium sulphate intravenous infusion was given in the postpartum period to all the patients, women were randomly allocated to group I (Single loading dose only), group II (12?h abbreviated protocol) or group III (24?h standard protocol) (n?=?80 in each group).

Results: There were no significant difference between the three groups as regards the incidence of eclampsia, elevated liver enzymes and low platelets syndrome, maternal ICU admission and; however The incidence of flushing was significantly higher in group III than group II and I (24 [30%] versus 12 [15%] versus 4 [5%]; p?<?0.001) respectively.

Conclusion: The pilot study demonstrates that the single-loading dose of postpartum magnesium sulphate is a promising alternative to the standard and the abbreviated protocol in preventing eclampsia; however, a large clinical trial is necessary to prove this.     

2,1-Benzothiazine – (quinolin/thiophen)yl hydrazone frameworks as new monoamine oxidase inhibitory agents; synthesis,in vitro and in silico investigation

Two series of new 2,1-benzothiazine derivatives have been synthesized by condensation of 4-hydrazono-1-methyl-3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (5) with 2-chloroquinoline-3-carbaldehydes and acetylthiophenes to acquire new heteroaryl ethylidenes 7(a–f) and 9(a–k) in excellent yields. After characterization by FTIR, ¹H NMR, ¹³C NMR and elemental analyses, the newly synthesized analogues were investigated against monoamine oxidase enzymes (MAO A and MAO B). The titled compounds exhibited activity in the lower micromolar range among which 9e was the most potent compound against MAO A with IC₅₀ of 1.04 ± 0.01 μM whereas 9h proved to be the most potent derivative against MAO B with an IC₅₀ value of 1.03 ± 0.17 μM. Furthermore, in vitro results were further endorsed by molecular docking studies to determine the interaction between the potent compounds and the enzyme active site. These newly synthesized compounds represent promising hits for the development of safer and potent lead molecules for therapeutic use against depression and other neurological diseases.

Two series of new 2,1-benzothiazine-heteroaryl ethylidene derivatives 7(a–f) and 9(a–k) have been synthesized in excellent yields and tested against MAOs.     

Rescuing fertility during COVID-19 infection: exploring potential pharmacological and natural therapeutic approaches for comorbidity,by focusing on NLRP3 inflammasome mechanism.

The respiratory system was primarily considered the only organ affected by Coronavirus disease 2019 (COVID-19). As the pandemic continues, there is an increasing concern from the scientific community about the future effects of the virus on male and female reproductive organs, infertility, and, most significantly, its impact on the future generation. The general presumption is that if the primary clinical symptoms of COVID-19 are not controlled, we will face several challenges, including compromised infertility, infection-exposed cryopreserved germ cells or embryos, and health complications in future generations, likely connected to the COVID-19 infections of parents and ancestors. In this review article, we dedicatedly studied severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virology, its receptors, and the effect of the virus to induce the activation of inflammasome as the main arm of the innate immune response. Among inflammasomes, nucleotide oligomerization domain-like receptor protein, pyrin domain containing 3 (NLRP3) inflammasome pathway activation is partly responsible for the inflicted damages in both COVID-19 infection and some reproductive disorders, so the main focus of the discussion is on NLRP3 inflammasome in the pathogenesis of COVID-19 infection alongside in the reproductive biology. In addition, the potential effects of the virus on male and female gonad functions were discussed, and we further explored the potential natural and pharmacological therapeutic approaches for comorbidity via NLRP3 inflammasome neutralization to develop a hypothesis for averting the long-term repercussions of COVID-19. Since activation of the NLRP3 inflammasome pathway contributes to the damage caused by COVID-19 infection and some reproductive disorders, NLRP3 inflammasome inhibitors have a great potential to be considered candidates for alleviating the pathological effects of the COVID-19 infection on the germ cells and reproductive tissues. This would impede the subsequent massive wave of infertility that may threaten the patients.     

Oxaliplatin-loaded nanoemulsion containing Teucrium polium L. essential oil induces apoptosis in Colon cancer cell lines through ROS-mediated pathway

Oxaliplatin (Oxa)-associated adverse side effects have considerably limited the clinical use of the drug in colon cancer therapy. Mutant p53 has diverse mutational profiles in colon cancer, and it influences the potencies of various chemotherapeutic drugs, including Oxa. Thus, it would be highly beneficial to identify an alternative therapeutic strategy that not only reduces the toxicity of Oxa, but also exerts a synergistic effect against colon cancers, regardless of their p53 profiles. The present study was aimed at preparing and optimizing Teucrium polium L. essential oil nanoemulsion (TPO-NANO) and investigating its effect on the sensitivity of colon cancer cells with differences in p53 status (HCT116 wild-type and HT-29 mutant-type) to Oxa. The viability of treated cells was determined and the combination index (CI) was calculated. Morphological changes were determined under inverted microscopy, while percentage apoptosis was assayed using flow cytometry. Intracellular ROS and the protein levels of p53 and Bax were measured. The colony-forming potential of treated cells was determined using colony assay. The size of TPO-NANO was markedly increased from 12.90 ± 0.04 nm to 14.47 ± 0.53 nm after loading Oxa (p ≤ 0.05). The combination (Oxa + TPO-NANO) produced a synergetic effect in HCT116 and HT-29, with CI of 0.94 and 0.88, respectively. Microscopic examination and flow cytometric analysis revealed that cells treated with Oxa + TPO-NANO had a higher percentage of apoptosis than cells exposed to monotherapy. Cumulatively, Oxa exerted an apoptotic effect on wild or mutant p53 colon cancer cells when combined with TPO-NANO, through a mechanism involving ROS-mediated mitochondrial apoptosis.     

Hypertrophic lichen planus on lip mimicking SCC

The lichen planus (LP) is an inflammatory and immune‐mediated disorder that can affect the hair, mucous membranes, nails, and skin. Lichen planus rarely affects the lips. In cases of lip involvement, it presents as radiated streaks, lace‐like papules, and erosions. There is no report of lip LP presenting as hypertrophic plaque. Here, we report interesting and rare clinical presentations of LP in a 45‐year‐old male patient that presented with a verrucous hyperkeratotic plaque on the lower lip mimicking squamous cell carcinoma. However, oral examination revealed, reticulated white patches on the bilateral buccal mucosa, and a biopsy of the lip lesion revealed lichenoid dermatitis which led to the diagnosis of hypertrophic lichen planus. Familiarity with the different clinical presentations of LP and its variants is essential for prompt diagnosis and effective treatment.     

Neurodegenerative disorder and diffuse brain calcifications due to FARSB mutation in two siblings

Pathogenic mutations in the FARSB gene are associated with neurodevelopmental disorder involving the brain, liver, and lungs. We report genetic analysis of a family including two affected members with this disorder, which revealed a homozygous pathogenic missense variant, FARSB: {"type":"entrez-nucleotide","attrs":{"text":"NM_005687.4","term_id":"743405629","term_text":"NM_005687.4"}}NM_005687.4:c.853G > A:p.E285K in both affected patients. The parents were heterozygous for this variant.     

An update on therapies for the treatment of diabetes-induced osteoporosis

Introduction: Currently, 424 million people aged between 20 and 79 years worldwide are diabetic. More than 25% of adults aged over 65 years in North America have Type 2 diabetes mellitus (DM). Diabetes-induced osteoporosis (DM-OS) is caused by chronic hyperglycemia, advanced glycated end products and oxidative stress. The increase in the prevalence of DM-OS has prompted researchers to develop new biological therapies for the management of DM-OS.

Areas covered: This review covered the current and novel biological agents used in the management of DM-OS. Data were retrieved from PubMed, Scopus, American Diabetes Association and International Osteoporosis Foundation websites, and ClinicalTrials.gov. The keywords for the search included: DM, osteoporosis, and management.

Expert opinion: Several biological molecules have been examined in order to find efficient drugs for the treatment of DM-OS. These biological agents include anti-osteoporosis drugs: net anabolics (parathyroid hormone/analogs, androgens, calcilytics, anti-sclerostin antibody), net anti-resorptive osteoporosis drugs (calcitonin, estrogen, selective estrogen receptor modulators, bisphosphonates, RANKL antibody) and anti-diabetic drugs (alpha glucosidase inhibitors, sulfonylureas, biguanides, meglitinides, thiazolidinediones, GLP-1 receptor agonists, dipeptidylpeptidase-4 inhibitors, sodium glucose co-transporter-2 inhibitors, insulin). Biological medications that effectively decrease hyperglycemia and, at the same time, maintain bone health would be an ideal drug/drug combination for the treatment of DM-OS.