Search Results (5)

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable disease that is typically observed in patients with osteoporosis or tumors that have been treated with either bisphosphonate (BP) or antiangiogenic medicine. The mechanism of MRONJ pathogenesis remains unclear, and no effective definitive treatment modalities have been reported to date. Previous reports have indicated that a single injection of benidipine, an antihypertensive calcium channel blocker, in the vicinity of a tooth extraction socket promotes wound healing in healthy rats. The present study was conducted to elucidate the possibility of using benidipine to promote the healing of MRONJ-like lesions. In this study, benidipine was administered near the site of MRONJ symptom onset in a model rat, which was then sacrificed two weeks after benidipine injection, and analyzed using histological sections and CT images. The analysis showed that in the benidipine groups, necrotic bone was reduced, and soft tissue continuity was recovered. Furthermore, the distance between epithelial edges, length of necrotic bone exposed in the oral cavity, necrotic bone area, and necrotic bone ratio were significantly smaller in the benidipine group. These results suggest that a single injection of benidipine in the vicinity of MRONJ-like lesions can promote osteonecrotic extraction socket healing. Full article

The development of an environmentally friendly analytical technique for simultaneous measurement of medicines with large concentration differences is difficult yet critical for environmental protection. Hence, in this work, new manipulated UV-spectroscopic methods with high scaling factors were established for concurrent quantification of telmisartan (TEL) and benidipine (BEN) in fixed-dose combinations. Two different methods were developed and established by calculation of peak height at zero crossing point of second derivative and the ratio of first derivative spectra with a scaling factor of 200 and 100, respectively. The absorption difference between the peaks and troughs of the ratio spectra, as well as continuous subtraction from ratio spectra, were established as additional methods. In addition, new procedures were validated using ICH recommendations. The proposed methods’ linearity curves were constructed in the range of 0.5–10 µg mL⁻¹ and 1–30 µg mL⁻¹ for BEN and TEL, respectively, under optimized conditions. Furthermore, both the detection (0.088–0.139 µg mL⁻¹ for BEN and 0.256–0.288 µg mL⁻¹ for TEL) and quantification limits (0.293–0.465 µg mL⁻¹ for BEN and 0.801–0.962 µg mL⁻¹ for TEL) were adequate for quantifying both analytes in the formulation ratios. The accuracy and precision were confirmed by the good recovery percent (98.37%–100.6%), with low percent relative error (0.67%–1.70%) and less than 2 percent relative standard deviation, respectively. The specificity of the methods was proven by accurate and precise outcomes from the standard addition method and analysis of laboratory mixed solutions with large differences in concentrations of both analytes. Finally, the BEN and TEL content of the formulations was determined simultaneously without prior separation using these first ever reported spectroscopic methods. Furthermore, developed UV derivative spectroscopic methods demonstrated high greenness and whiteness when compared to the reported HPLC methods. These findings show that the projected methods were effective, practical, and environmentally acceptable for quality control of BEN and TEL in multicomponent formulations. Full article

Drug resistance in epithelial ovarian cancer (EOC) is reportedly attributed to the existence of cancer stem cells (CSC), because in most cancers, CSCs still remain after chemotherapy. To overcome this limitation, novel therapeutic strategies are required to prevent cancer recurrence and chemotherapy-resistant cancers by targeting cancer stem cells (CSCs). We screened an FDA-approved compound library and found four voltage-gated calcium channel blockers (manidipine, lacidipine, benidipine, and lomerizine) that target ovarian CSCs. Four calcium channel blockers (CCBs) decreased sphere formation, viability, and proliferation, and induced apoptosis in ovarian CSCs. CCBs destroyed stemness and inhibited the AKT and ERK signaling pathway in ovarian CSCs. Among calcium channel subunit genes, three L- and T-type calcium channel genes were overexpressed in ovarian CSCs, and downregulation of calcium channel genes reduced the stem-cell-like properties of ovarian CSCs. Expressions of these three genes are negatively correlated with the survival rate of patient groups. In combination therapy with cisplatin, synergistic effect was shown in inhibiting the viability and proliferation of ovarian CSCs. Moreover, combinatorial usage of manidipine and paclitaxel showed enhanced effect in ovarian CSCs xenograft mouse models. Our results suggested that four CCBs may be potential therapeutic drugs for preventing ovarian cancer recurrence. Full article

Unlike chyloperitoneum associated with clinical conditions including cancer, cirrhosis, and traumatic surgery, calcium channel blocker (CCB)-associated chyloperitoneum is rarely discussed in comprehensive studies on chyloperitoneum. We aimed to investigate the prevalence and characteristics of CCB-associated chyloperitoneum in peritoneal dialysis (PD) patients. The MEDLINE, Embase, CENTRAL, CiNii, and RISS databases were systematically searched for clinical studies on CCB-associated chyloperitoneum in PD patients published up to 31 July 2018. A total of 17 studies (four cohort studies, one case series, and 12 case reports) were selected. Eight CCBs, namely amlodipine, benidipine, diltiazem, lercanidipine, manidipine, nifedipine, nisoldipine, and verapamil, were reported to be associated with chyloperitoneum; manidipine and lercanidipine were the most frequently reported. The average prevalence of chyloperitoneum for lercanidipine was 25.97% in three cohort studies, two of which had a moderate or high risk of bias. Most of the studies revealed chyloperitoneum development within 4 days of initiation of CCB therapy and chyloperitoneum disappearance within 24 h of CCB withdrawal. The results of this study emphasise on the need for awareness among healthcare professionals regarding CCB-associated chyloperitoneum in PD patients. Further studies elucidating the causality and clinical implication of CCB-associated chyloperitoneum are needed. Full article

Tumor treating fields (TTFields) represent a novel FDA-approved treatment modality for patients with newly diagnosed or recurrent glioblastoma multiforme. This therapy applies intermediate frequency alternating electric fields with low intensity to the tumor volume by the use of non-invasive transducer electrode arrays. Mechanistically, TTFields have been proposed to impair formation of the mitotic spindle apparatus and cytokinesis. In order to identify further potential molecular targets, here the effects of TTFields on Ca²⁺-signaling, ion channel activity in the plasma membrane, cell cycle, cell death, and clonogenic survival were tested in two human glioblastoma cell lines in vitro by fura-2 Ca²⁺ imaging, patch-clamp cell-attached recordings, flow cytometry and pre-plated colony formation assay. In addition, the expression of voltage-gated Ca²⁺ (Ca_v) channels was determined by real-time RT-PCR and their significance for the cellular TTFields response defined by knock-down and pharmacological blockade. As a result, TTFields stimulated in a cell line-dependent manner a Ca_v1.2-mediated Ca²⁺ entry, G₁ or S phase cell cycle arrest, breakdown of the inner mitochondrial membrane potential and DNA degradation, and/or decline of clonogenic survival suggesting a tumoricidal action of TTFields. Moreover, inhibition of Ca_v1.2 by benidipine aggravated in one glioblastoma line the TTFields effects suggesting that Ca_v1.2-triggered signaling contributes to cellular TTFields stress response. In conclusion, the present study identified Ca_v1.2 channels as TTFields target in the plasma membrane and provides the rationale to combine TTFields therapy with Ca²⁺ antagonists that are already in clinical use. Full article