Development of Sustained Release Formulations Based on Lipid-Liquid Crystal to Control the Release of Deoxycholate: In Vitro and In Vivo Assessment.

Subcutaneous injections of phosphatidylcholine (PC), sodium deoxycholate (NADC), and a mixture of them were found to be an effective option for treating cellulite. However, it is noteworthy that the injection of NADC may result in inflammation as well as necrosis in the injection area. The preparation of a sustained release formulation based on lipid-liquid crystal that controls the release of NADC could be a potential solution to address the issue of inflammation and necrosis at the site of injection. To present a practical and validated approach for accurately determining the concentration of NADC in LLC formulations, spectrofluorimetry was used based on the International Council for Harmonization (ICH) Q2 guidelines. Based on the validation results, the fluorometric technique has been confirmed as a reliable, efficient, and economical analytical method for quantifying NADC concentrations. The method demonstrated favorable attributes of linearity, precision, and accuracy, with an r2 value of 0.999. Furthermore, it exhibited excellent interday and intraday repeatability, with RSD values below 4%. The recovery percentages ranged from 97 to 100%, indicating the method's ability to accurately measure NADC concentrations. The subcutaneous injection of the LLC-NADC demonstrated a reduction in inflammation and tissue necrosis in skin tissue, along with an increase in fat lysis within 30 days, when compared to the administration of only NADC solution. Moreover, the histopathological assessment confirmed that the use of the LLC formulation did not result in any detrimental side effects for kidney or heart tissue.

Novel scaffold platforms for simultaneous induction osteogenesis and angiogenesis in bone tissue engineering: a cutting-edge approach.

Despite the recent advances in the development of bone graft substitutes, treatment of critical size bone defects continues to be a significant challenge, especially in the elderly population. A current approach to overcome this challenge involves the creation of bone-mimicking scaffolds that can simultaneously promote osteogenesis and angiogenesis. In this context, incorporating multiple bioactive agents like growth factors, genes, and small molecules into these scaffolds has emerged as a promising strategy. To incorporate such agents, researchers have developed scaffolds incorporating nanoparticles, including nanoparticulate carriers, inorganic nanoparticles, and exosomes. Current paper provides a summary of the latest advancements in using various bioactive agents, drugs, and cells to synergistically promote osteogenesis and angiogenesis in bone-mimetic scaffolds. It also discusses scaffold design properties aimed at maximizing the synergistic effects of osteogenesis and angiogenesis, various innovative fabrication strategies, and ongoing clinical studies.

Involvement of T-type calcium channels in the mechanism of low dose morphine-induced hyperalgesia in adult male rats.

It has been shown that systemic and local administration of ultra-low dose morphine induced a hyperalgesic response via mu-opioid receptors. However, its exact mechanism(s) has not fully been clarified. It is documented that mu-opioid receptors functionally couple to T-type voltage dependent Ca+2 channels. Here, we investigated the role of T-type calcium channels, amiloride and mibefradil, on the induction of low-dose morphine hyperalgesia in male Wistar rats. The data showed that morphine (0.01 µg i.t. and 1 µg/kg i.p.) could elicit hyperalgesia as assessed by the tail-flick test. Administration of amiloride (5 and 10 µg i.t.) and mibefradil (2.5 and 5 µg i.t.) completely blocked low-dose morphine-induced hyperalgesia in spinal dorsal horn. Amiloride at doses of 1 and 5 mg/kg (i.p.) and mibefradil (9 mg/kg ip) 10 min before morphine (1 µg/kg i.p.) inhibited morphine-induced hyperalgesia. Our results indicate a role for T-type calcium channels in low dose morphine-induced hyperalgesia in rats.

Infective endocarditis uncovered a very rare congenital heart disease.

In this article, we introduced a case of rare congenital anomalies that was asymptomatic until adulthood and was complicated by infective endocarditis and dissection of aortic valve leaflet.

The Effects of Folic Acid on Testicular Histology, Sperm Quality, and Spermatogenesis Indices Following 3,4-Methylenedioxymethamphetamine Exposure in Adult Male Rats.

BACKGROUND: There is an increasing concern over acute exposure of amphetamine and its derivative such as 3,4-methylenedioxymethamphetamine (MDMA) on male reproductive toxicity. Supplementary vitamins can reduce the oxidative stresses and repair the damages on reproductive organs. This experimental study was conducted to evaluate the effects of folic acid (FA) on reproductive indices, the antioxidant enzyme activities, and histological changes of testis on adult male rats treated by MDMA. METHODS: This experimental study was conducted on adult male Wistar rats. Animals were divided into 4 groups: control, MDMA, FA, and MDMA + FA. Animals received a dose of 10 mg/kg of MDMA and 1 mg/kg of FA for 7 or 14 days. Rats were anesthetized and sperm quality parameters (number, concentration, motility, and morphology), spermatogenesis indices [the mean seminiferous tubule diameter (MSTD), spermiogenesis index (SI), repopulation index (RI), and tubular differentiation index (TDI)], changes on testicular structure, antioxidant enzyme activities of catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) beside serum level of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were measured. Data were analyzed, using the one-way analysis of variance (ANOVA) and SPSS software. FINDINGS: MDMA (both 7 and 14 days) caused significant changes in sperm quality (P < 0.001), spermatogenesis indices (P < 0.001), testicular histopathology, and level of LH, FSH, testosterone beside the antioxidant enzyme activities (SOD, CAT, and MDA) (P < 0.001). Supplementation of FA in association with MDMA partially reversed these parameters and made them close to the control group. CONCLUSION: The results suggested that FA could reduce the adverse effect of MDMA on reproductive ability in adult male rats.

Effects of Subacute Administration of Co-Trimoxazole and Folic Acid on Ovarian Tissue in Adult Female Rats.

BACKGROUND: Previous studies have reported the antifertility activities of sulfonamides. This study was designed to evaluate the effects of co-trimoxazole and its co-administration with folic acid on ovarian tissue in female rats. METHODS: A total of 54 rats were randomly divided into 9 groups (n=6). Group I served as the control and group II (vehicle) received saline. Other groups, III to IX, received co-trimoxazole (30, 60, and 120 mg/kg; i.p.), folic acid (1 mg/kg; i.p.) or their combination for 14 days, respectively. The oocytes were obtained from each group at the end of the 14th days and scored for maturational status as germinal vesicle (GV), metaphase I (MI), or metaphase II (MII). The number of primordial follicle (PrF), primary follicle (PF), and secondary follicle in formalin-fixed ovaries were counted under light microscopy. The data were analyzed by one-way ANOVA followed by post-hoc Dunnet test using SPSS statistical software (version 17.0). Results were considered statistically significant at P<0.05. RESULTS: Co-trimoxazole (60 and 120 mg/kg) treatment for 14 days caused a significant decrease in the number of GV (P=0.02, P<0.001), MI and MII (P=0.03, P<0.001), a significant increase in structural abnormalities, including PrF, PF and secondary follicle (P<0.001) as well as congestion, inflammation and necrosis of ovarian tissue compared to the vehicle group. Folic acid co-administration with co-trimoxazole reversed partially all these parameters compared to the co-trimoxazole group (P<0.001). CONCLUSION: The data showed the adverse effects of co-trimoxazole on the ovarian maturational status and tissue structure which was reversed partially by folic acid co-administration in rats.

Effects of Methamphetamine on Testes Histopathology and Spermatogenesis Indices of Adult Male Rats.

BACKGROUND: Methamphetamine (MAMP) as a recreational drug has devastating effects on the central nervous system (CNS). Several studies have shown that MAMP has inhibitory effects on oogenesis and spermatogenesis, and causes impaired fertility. This study designed to investigate the effect of mAM Padministration on histological changes and spermatogenesis indices in the testis of adult male rats. METHODS: In this experimental study, 50 male Wistar rats were randomly divided into control (received no treatment, n = 10), vehicle (received saline for 7 and 14 days, n = 20), and experimental group [received MAMP, 5 ml/kg, intraperitoneal (IP) for 7 and 14 days, n = 20]. Testicular tissue samples were stained by hematoxylin and eosin (H&E) technique. For histological study, we counted the number of spermatogonia, spermatocytes and Leydig cells. Spermatogenesis indices which include: tubular differentiation index (TDI), spermiogenesis index (SI), repopulation index (RI) and the mean seminiferous tubules diameter (MSTD) were studied. Data were analyzed by one-way ANOVA, using SPSS software. P < 0.05 was considered statistically significant. FINDINGS: This study showed that MAMP caused a significant decrease in number of seminiferous tubules cells and spermatogenesis in treated group compared with the control group. Moreover, results showed a significant decrease in spermatogenesis indices including TDI, SI, RI, and MSTD in 14th day, compared to control group (P < 0.001). CONCLUSION: The data showed the adverse effects of MAMP administration (for 7 and 14 days) on testes structure and spermatogenesis indices in rat testis tissue. The underlying mechanism(s) needs further investigation.

Effects of administration of co-trimoxazole and folic acid on sperm quality and histological changes of testes in male rats.

BACKGROUND: Male infertility has been reported following long-term sulfasalazine, however, the precise effects of co-trimoxazole on sperm quality is controversial. OBJECTIVE: In this study, we evaluated the effects of co-trimoxazole and its co-administration with folic acid on sperm quality and histological changes of testes in male rats. MATERIALS AND METHODS: In this experimental study, 136 male Wistar rats were divided into 9 groups: I (control), II (vehicle) received saline, III: received folic acid (1 mg/kg /daily i.p., and IV- IX received co-trimoxazole (30, 60, and 120 mg/kg/daily; i.p.)+folic acid (1 mg/kg/daily; i.p.) for 14 or 28 days. Sperm samples were obtained from each group at the end of 14th and 28th days. Sperm numbers, motility, and viability were evaluated on a hemocytometer. Hematoxylin and Eosin stained testes were done for evaluation ofthe number of Leydig cells, vascularity, spermatids, spermatocytes, and means of seminiferous tubules diameter under light microscopy. RESULTS: Co-trimoxazole treatment for either 14 or 28 days caused a significant decrease in the percentage of sperm number, motility, and viability (p<0.001) compared to the control group. Also, high doses of co-trimoxazole caused a significant decrease in testes structural abnormalities means of seminiferous tubules diameter, spermatids, and spermatogonia) compared to the vehicle group (p<0.001). Folic acid co-administration with co-trimoxazole partially reversed the decrease in sperm quality and structural abnormalities of high doses of co-trimoxazole (60 and 120 mg/kg/daily) (p<0.001). CONCLUSION: The data showed the adverse effects of co-trimoxazole on sperm quality and testes morphology which was protected partially by folic acid co-administration in rats. The underlying mechanism (s) needs further investigations.

The Effects of Methanolic Extract of Melissa officinalis on Experimental Gastric Ulcers in Rats.

BACKGROUND: Melissa officinalis (MO) has potent antioxidant activity. Recent research has demonstrated the anti-ulcer properties of some medicinal plants through their antioxidant properties. OBJECTIVES: The aim of this study was to evaluate the effects of methanolic extracts of MO on experimental gastric ulcers in rats. MATERIALS AND METHODS: Male Wistar rats (200 - 250 g) were starved for 24 hours prior to the induction of gastric ulceration by either indomethacin (48 mg/kg/oral) or water immersion restraint (WIR) stress. Experimental rats received either ranitidine (25 mg/kg) or MO extract (150, 300 and 450mg/kg) orally 2 hours prior to WIR stress or indomethacin treatment, for the evaluation of their gastroprotective effects. The control group received the same volume of saline. Gastric lesions were scored according to the surface of lesions on the ulcer index. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) were determined as measures of antioxidant defense, and malondialdehyde (MDA) was determined to measure tissue oxidation. RESULTS: MO extract (150 and 300 mg/kg) significantly decreased the ulcer index in both the indomethacin (1.3 ± 0.09 and 1.5 ± 0.19, respectively) and WIR stress groups (1.5 ± 0.17 and 1.5 ± 0.22, respectively), as compared to the control rats (2.5 ± 0.28) (P < 0.01). MO extract (450 mg/kg) significantly reduced ulcer index readings in WIR stress rats (1.8 ± 0.31 vs. 2.4 ± 0.15 in the WIR group), however, MO extract at a dose of 450 mg/kg did not prevent indomethacin-induced gastric ulceration (2.4 ± 0.26). There was no significant difference in the ulcer index for MO extract- (150 and 300 mg/kg) and ranitidine-treated rats (P > 0.05). Also, MO extract (150 and 300 mg/kg) significantly reduced MDA serum levels (0.69 ± 0.6 µmol/L and 0.85 ± 0.24 µmol/L, respectively, vs. 4.5 ± 1.9 µmol/L in the saline group) and significantly increased antioxidants' SOD activities (296.3 ± 146.4 U/mL and 561.4 ± 120 U/mL, respectively, vs. 190.2 ± 63.8U/mL in the control group) and GPX levels (8273 ± 3049 U/mL and 14574 ± 5012 U/mL, respectively), compared to the control (3236 ± 1699 U/mL). CONCLUSIONS: Our results showed that MO extract may have a gastroprotective effect against experimental gastric ulcers in rats. The exact mechanism has not yet been determined, but it may be due to enhancing enzymatic antioxidant defenses and inhibiting lipid peroxidation.

Comparison of the clinical outcomes of connective tissue and acellular dermal matrix in combination with double papillary flap for root coverage: A 6-month trial.

BACKGROUND: Different techniques have been proposed for the treatment of gingival recession. The majority of current procedures use autogenous soft-tissue grafts, which are associated with morbidity at the donor sites. Acellular dermal matrix (ADM) Alloderm is an alternative donor material presented to reduce related morbidity and provide more volume of the donor tissue. This study aimed to evaluate the effectiveness of an ADM allograft for root coverage and to compare it with a connective tissue graft (CTG), when used with a double papillary flap. MATERIALS AND METHODS: Sixteen patients with bilateral class I or II gingival recessions were selected. A total of 32 recessions were treated and randomly assigned into the test and contralateral recessions into the control group. In the control group, the exposed root surfaces were treated by the placement of a CTG in combination with a double papillary flap; and in the test group, an ADM allograft was used as a substitute for palatal donor tissue. Probing depth, clinical attachment level, width of keratinized tissue (KT), recession height and width were measured before, and after 2 weeks and 6 months of surgery. RESULTS: There were no statistically significant differences between the test and control groups in terms of recession reduction, clinical attachment gain, and reduction in probing depth. The control group had a statistically significant increased area of KT after 6 months compared to the test group. CONCLUSION: ADM allograft can be considered as a substitute for palatal donor tissue in root coverage procedure.