Coumarin-based bioactive compounds: facile synthesis and biological evaluation of coumarin-fused 1,4-thiazepines

As part of our ongoing studies on the synthesis of bioactive coumarin compounds, we synthesized a series of new coumarin-fused 1,4-thiazepines using a simple method. The biological activity of target compounds along with 3-(2-hydroxybenzylidene)chroman-2,4-dione intermediates was screened by evaluation of their antioxidant and cytotoxic activities. The antioxidant activity was assessed using two methods, namely, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method and ferric reducing antioxidant power (FRAP) assay. 4-Methoxyphenolic compound 5d in thiazepine series showed the most potent scavenging activity, while the 4-bromophenolic derivative 5b was the most efficient compound in FRAP assay. Also, the result of cytotoxic evaluation using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay demonstrated that compound 5b is at least twofold more potent than etoposide against MCF-7, SK-N-MC, and MDA-MB 231 cell lines.     

Polymerization behavior and thermal characteristics of two new composites at five temperatures: refrigeration to preheating

PURPOSE

Heat of composite polymerization (HP) indicates setting efficacy and temperature increase of composite in clinical procedures. The purpose of this in vitro experimental study was to evaluate the effects of 5 temperatures on HP of two new composites.

MATERIALS AND METHODS

From each material (Core Max II [CM] and King Dental [KD]), 5 groups of 5 specimens each were prepared and their total HPs (J/gr) were measured and recorded, at one of the constant temperatures 0℃, 15℃, 23℃, 37℃ and 60℃ (2 × 5 × 5 specimens) using a differential scanning calorimetry (DSC) analyzer. The data were analyzed using a two-way ANOVA, a Tukey''s test, an independent-samples t-test, and a linear regression analysis (α=0.05).

RESULTS

No polymerization reactions occurred at 0℃; then this temperature was excluded from statistical analyses. The mean HP of the remaining 20 KD specimens was 20.5 ± 14.9 J/gr, while it was 40.7 ± 12.9 J/gr for CM. The independent-samples t-test showed that there were significant differences between the HP of the two materials at the temperatures 15℃ (P=.0001), 23℃ (P=.0163), 37℃ (P=.0039), and 60℃ (P=.0106). Linear regression analysis showed statistically significant correlations between environment temperatures and HP of CM (R²=0.777).

CONCLUSION

Using CM is advantageous over conventional composite because of its better polymerization capacity. However due to its high HP, further studies should assess its temperature increase in vivo. Preheating KD is recommended. Refrigerating composites can negatively affect their polymerization potential.     

Detection of hepatitis B virus variants in HBV monoinfected and HBV/HIV coinfected Iranian patients under lamivudine treatment

Chronic hepatitis B affects nearly 10% of HIV-infected patients. Hepatitis B virus (HBV) infection is a dynamic disease and coinfection with HIV impacts directly on the outcome of HBV infection, considerably complicating its natural history, diagnosis, and management. The aim of this study was to compare two cohorts of HBV monoinfected and HBV/HIV coinfected Iranian patients undergoing long-term lamivudine therapy from the clinical and virological aspects, as well as the frequency of detected mutations in HBV genome. To this end, HBV Pol/S regions from 72 patients were PCR-amplified and directly sequenced. Phylogenetic analysis indicated a 40-times higher risk of coinfection with ayw3 subtype of HBV genotype D rather than ayw2 subtype [P<0.001, odd: 40.66, CI: 95 % (4.69-352.23)]. While no resistance mutation was detected in HBV/HIV coinfected cohort, LAM-resistance mutations (rtM204I/V in YMDD and rtL180M in FLLA polymerase motifs) were identified in 30% (9 out of 30) and 16.66% (5 out of 30) of HBV monoinfected patients (P<0.05). Moreover, several mutations (sP105A, sI110S/L, sS136Y and sP127T/L) with significant differences in the frequency were identified in the S region of both cohorts. Finally, this study found strong correlation between the type of infection (mono or coinfection) and characteristics like patient gender, ALT levels, HBV-DNA levels and HBV subtypes. These results pointed to the importance of determination of HBV variants in the management of patients and suggested that in contrary to HBV monoinfections, LAM may be still an appropriate drug for the treatment of HBV in HBV/HIV coinfected patients; however, further studies to clarify the role of HIV in HBV LAM-resistance mutations are required.     

Synthesis and in vitro anti-Helicobacter pylori activity of N-[5-(5-nitro-2-heteroaryl)-1,3,4-thiadiazol-2-yl]thiomorpholines and related compounds

Synthesis and in vitro anti-Helicobacter pylori activity of N-[5-(5-nitro-2-heteroaryl)-1,3,4-thiadiazol-2-yl]thiomorpholines 5-7(a-c) and some related compounds 8a-c and 9a-c were described. The anti-H. pylori activity of target compounds along with commercially available antibiotics such as metronidazole and amoxicillin was evaluated by comparing the inhibition zone diameters determined by the paper disc diffusion bioassay. From our bioassay results against 20 clinical isolates, it is evident that most compounds still had strong activity at 4 and 2mug/disc (average of inhibition zone >20mm) while metronidazole had little activity at these doses. Nitrofuran analog 7b containing thiomorpholine S,S-dioxide moiety was the most potent compound tested.     

The effect of topical piperine combined with narrowband UVB on vitiligo treatment: A clinical trial study

Vitiligo is the most common acquired hypopigmentary disease in the community. Piperine as an herbal extract derived from black pepper has strong impact on the melanocyte proliferation and adverse side effects less than synthetic drugs such as corticosteroids. For the first time, this study was aimed to evaluate the effect of topical piperine combined with narrowband ultraviolet B (NB‐UVB) on vitiligo treatment. In this double‐blind clinical trial, 63 patients with facial vitiligo were randomly divided into 2 groups: treated with piperine (case) and placebo (control). Also, both groups received NB‐UVB phototherapy every other day for 3 months. In the case group, 10 patients have burning sensation on their skin areas (p value = .002). Also, redness of the treated areas was observed in 6 patients (p value = .028). Both side effects were temporary. Regarding repigmentation at time intervals of 1, 2, and 3 months after treatment, its level in the case group was significantly higher than the control group (p value < .001). Based on our findings, the combination therapy with NB‐UVB/topical piperine has more influence on facial vitiligo than that of NB‐UVB alone. It could be concluded that the simultaneous use of NB‐UVB and topical piperine has a remarkable effect on treatment of vitiligo.     

Acitretin-induced spiny follicular hyperkeratosis

Spiny follicular hyperkeratosis (SFH) is follicular flesh-colored hyperkeratotic spicules that are linked to different situations including drug reactions. Previously suspected drugs are BRAF inhibitors and cyclosporine. We described a 51-year-old psoriasis patient with SFH who had been using acitretin.     

Complex Genitourinary Duplication Affecting Neurourologic and Urodynamic Findings: Report of a Case and Review of the Literature

BackgroundComplete duplication of the bladder and urethra is a rare congenital anomaly and usually occurs in association with other organ anomalies. We report a case of complete bladder duplication associated with multiple non-genitourinary anomalies.CaseA 10-year-old girl presented with urinary incontinence and recurrent episodes of febrile urinary tract infections. Simultaneous right and left bladder urodynamic study was performed and revealed bilateral decreased bladder compliance associated with hyperreflexia. The patient underwent reconstructive surgery with combination of the 2 bladders and closure of the right incompetent bladder neck.Summary and conclusionManagement of bladder duplication is directed towards creating an unobstructed urinary tract, preventing infections, and achieving urinary continence. Neurourologic and urodynamic assessment is of utmost importance especially when concomitant spinal anomaly exists. Furthermore, these patients should be observed lifelong as alteration in bladder function may occur.     

Utero-cutaneous fistula after caesarean section secondary to red degeneration of intramural fibroid

A 33 year-old woman had an emergency caesarean section for retained second twin which was complicated by utero-cutaneous fistula due to red degeneration of intramural fibroid. The utero-cutaneous communication was demonstrated by an examination under anaesthesia using dye test. She then underwent excision of the fistula tract and myomectomy. She recovered well following the surgery. This is the first case of utero-cutaneous fistula where the communication is between the endometrial cavity and skin lesion via a necrotic intramural fibroid following caesarean section. Fistulogram might fail to demonstrate the communication. In highly suspected case, other modalities of investigations could be utilised.