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The Journal of Biological Chemistry 2021The mitochondrial calcium uniporter (MCU) and cyclophilin D (CyD) are key players in induction of the permeability transition pore (PTP), which leads to mitochondrial...
The mitochondrial calcium uniporter (MCU) and cyclophilin D (CyD) are key players in induction of the permeability transition pore (PTP), which leads to mitochondrial depolarization and swelling, the major signs of Ca-induced mitochondrial damage. Mitochondrial depolarization inhibits ATP production, whereas swelling results in the release of mitochondrial pro-apoptotic proteins. The extent to which simultaneous deletion of MCU and CyD inhibits PTP induction and prevents damage of brain mitochondria is not clear. Here, we investigated the effects of MCU and CyD deletion on the propensity for PTP induction using mitochondria isolated from the brains of MCU-KO, CyD-KO, and newly created MCU/CyD-double knockout (DKO) mice. Neither deletion of MCU nor of CyD affected respiration or membrane potential in mitochondria isolated from the brains of these mice. Mitochondria from MCU-KO and MCU/CyD-DKO mice displayed reduced Ca uptake and diminished extent of PTP induction. The Ca uptake by mitochondria from CyD-KO mice was increased compared with mitochondria from WT mice. Deletion of CyD prevented mitochondrial swelling and resulted in transient depolarization in response to Ca, but it did not prevent Ca-induced delayed mitochondrial depolarization. Mitochondria from MCU/CyD-DKO mice did not swell in response to Ca, but they did exhibit mild sustained depolarization. Dibucaine, an inhibitor of the Ca-activated mitochondrial phospholipase A2, attenuated and bovine serum albumin completely eliminated the sustained depolarization. This suggests the involvement of phospholipase A2 and free fatty acids. Thus, in addition to induction of the classical PTP, alternative deleterious mechanisms may contribute to mitochondrial damage following exposure to elevated Ca.
Topics: Animals; Brain; Calcium; Calcium Channels; Peptidyl-Prolyl Isomerase F; Gene Knockout Techniques; Mice; Mice, Knockout; Mitochondria; Mitochondrial Proteins
PubMed: 33864812
DOI: 10.1016/j.jbc.2021.100669 -
Molecular Pharmaceutics Jun 2023In this study, we investigated the effects of drugs on membrane function in which lipid peroxidation was inhibited by the antioxidant Trolox (TRO) in liposomes...
In this study, we investigated the effects of drugs on membrane function in which lipid peroxidation was inhibited by the antioxidant Trolox (TRO) in liposomes containing egg yolk lecithin. Local anesthetics (LAs), such as lidocaine (LID) and dibucaine (DIB), were used as model drugs. The effect of LAs on the inhibitory activity of TRO was evaluated by calculating the p from the inhibition constant calculated by curve fitting. p indicates the strength of TRO membrane protective function. p indicates the strength of LA activity. LAs inhibited lipid peroxidation in a dose-dependent manner and decreased p. The effect of DIB on p was 1.9 times more than that of LID. This result indicated that LA may improve the fluidity of the membrane, which may facilitate the migration of TRO from the membrane to the liquid phase. As a result, TRO is less likely to suppress lipid peroxidation within the lipid membrane, possibly resulting in a decrease in p. The effect of TRO on p was found to be similar in both, indicating that it did not depend on the type of the model drug. These results suggest that our developed procedure successfully quantified the effects of LAs on lipid membrane functions. We were able to obtain the characteristics of model drugs independent of TRO by simultaneously measuring and analyzing the lipid peroxidation inhibitory activities of TRO and model drugs in liposomes.
Topics: Anesthetics, Local; Liposomes; Lipid Peroxidation; Antioxidants; Dibucaine; Lidocaine; Lipids
PubMed: 37104048
DOI: 10.1021/acs.molpharmaceut.2c01053 -
Journal of Pharmacy & Bioallied Sciences Jun 2021To compare and analyze the clinical adequacy of two topical anesthetic gels, Precaine (8% lidocaine + 0.8% dibucaine) and Precaine B (20% benzocaine) in children before...
AIM
To compare and analyze the clinical adequacy of two topical anesthetic gels, Precaine (8% lidocaine + 0.8% dibucaine) and Precaine B (20% benzocaine) in children before intraoral local anesthetic injections.
MATERIALS AND METHODS
This clinical study included thirty children who needed an inferior alveolar nerve block. They were divided into three groups: Group A: Precaine topical gel group, Group B: Precaine B topical gel Group, Group C: no anesthetic topical gel group (control group). These two effective topical gels were applied before giving intraoral local anesthesia, and afterward, the child's pain response was surveyed utilizing the Wong-Baker Faces Pain Rating Scale. The scores obtained were subjected to statistical analysis.
RESULTS
Intergroup comparison showed a significant mean difference between the control group and Precaine group ( > 0.05) as well as Precaine B group ( > 0.05). However, there is no significant difference obtained between Group A and Group B ( < 0.05).
CONCLUSION
It is psychologically and clinically beneficial to apply a topical anesthetic agent before injecting any intraoral anesthesia. In this study, both anesthetic gels showed a nonsignificant difference in reducing inferior alveolar injection pain, but Precaine B shows more promising results than Precaine.
PubMed: 34447172
DOI: 10.4103/jpbs.JPBS_772_20 -
Revista Brasileira de Ginecologia E... May 2021The diagnosis of genital ulcers remains a challenge in clinical practice. Lipschütz ulcer is a non-sexually transmitted rare and, probably, underdiagnosed condition,...
The diagnosis of genital ulcers remains a challenge in clinical practice. Lipschütz ulcer is a non-sexually transmitted rare and, probably, underdiagnosed condition, characterized by the sudden onset of vulvar edema along with painful necrotic ulcerations. Despite its unknown incidence, this seems to be an uncommon entity, with sparse cases reported in the literature. We report the case of an 11-year-old girl who presented at the emergency department with vulvar ulcers. She denied any sexual intercourse. The investigation excluded sexually transmitted infections, so, knowledge of different etiologies of non-venereal ulcers became essential. The differential diagnoses are extensive and include inflammatory processes, drug reactions, trauma, and malignant tumors. Lipschütz ulcer is a diagnosis of exclusion. With the presentation of this case report, the authors aim to describe the etiology, clinical course, and outcomes of this rare disease, to allow differential diagnosis of genital ulceration.
Topics: Administration, Topical; Anti-Infective Agents, Local; Child; Diagnosis, Differential; Dibucaine; Epstein-Barr Virus Infections; Female; Humans; Rare Diseases; Treatment Outcome; Ulcer; Vulvar Diseases
PubMed: 34077985
DOI: 10.1055/s-0041-1729147 -
BMC Psychiatry Mar 2021Poisoning and deaths by organo-phosphorous (OP) compounds are one of the major causes of death in developing and poor countries, and a common admission in the emergency...
BACKGROUND
Poisoning and deaths by organo-phosphorous (OP) compounds are one of the major causes of death in developing and poor countries, and a common admission in the emergency ward and the ICU. OP compounds act by irreversibly binding to pseudocholinesterase enzyme and hence prolong the apnea in patients being given suxamethonium. We present a unusual case of OP poisoning (OPP) in which prolonged apnea ensued in a patient of severe depression following MECT (modified electroconvulsive therapy) in which suxamethonium was used as muscle relaxant, in whom we were cautious of the side-effect of prior organophosphorus poisoning. Since the cases of OPP are very high worldwide, a thorough knowledge of the interaction of the action of the drug and the receptors on which it acts takes pride of place. This article highlights the nuances in the field of psychiatry and anaesthesia in diagnosis and management of prolonged apnea after ECT.
CASE PRESENTATION
A 53/F patient consumed OP 38 days prior to MECT. Since existing literature recommend a delay of 4 weeks and a subminimal dose of suxamethonium to prevent prolonged apnea, both these points were taken into consideration. Despite 38 days post exposure to OP, and a dose of succinylcholine of < 0.3 mg/kg, the patient remained apneic for 3 h. Suxamethionum apnea was managed with elective ventilation. After recovery, patient had no residual effect. Subsequently her pseudocholinesterase levels were done which were found to be very low.
CONCLUSION
This case is being presented to emphasize that behaviour of post synaptic receptors cannot be relied upon after OP poisoning and pseudocholinesterase levels needs to be mandatorily checked, irrespective of duration post-exposure. In strong suspects dibucaine number and fluoride number also needs to be estimated.
Topics: Apnea; Electroconvulsive Therapy; Female; Humans; Neuromuscular Depolarizing Agents; Organophosphate Poisoning; Poisoning; Succinylcholine
PubMed: 33691646
DOI: 10.1186/s12888-021-03150-0 -
Molecules (Basel, Switzerland) Aug 2022In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl-carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic...
In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl-carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic solid-phase extraction (MSPE) for the preconcentration of seven local anesthetic drugs (procaine, lidocaine, mepivacaine, oxybuprocaine, bupivacaine, tetracaine, and cinchocaine) from human plasma. The separation and determination of analytes were performed on high-performance liquid chromatography with UV detection. Several factors affected the extraction efficiency, such as the amount of adsorbents used, extraction time, sample pH, and optimization of elution conditions. Under optimal conditions, satisfactory linear relationships were obtained in the range of 0.02-5.00 mg/L, with the limits of detection (LOD) ranging from 0.003 mg/L to 0.008 mg/L. The recoveries of analytes for spiked human plasma were in the range of 82.0-108%. Moreover, the precision with intra-day and inter-day RSD values were obtained in the range of 1.5-7.7% and 1.5-8.3%. The results indicated that this method could determine the concentration of seven local anesthetic drugs in human plasma with high precision and repeatability and provide support for the clinical monitoring of the concentration of local anesthetic drugs in human plasma.
Topics: Anesthetics, Local; Chromatography, High Pressure Liquid; Humans; Magnetic Phenomena; Nanotubes, Carbon; Solid Phase Extraction
PubMed: 36080279
DOI: 10.3390/molecules27175509 -
Evidence-based Complementary and... 2022Alzheimer's disease (AD) is the most common type of dementia, and the abnormal hyperphosphorylation of the tau protein is the main component of its pathogenesis. Calpain...
Alzheimer's disease (AD) is the most common type of dementia, and the abnormal hyperphosphorylation of the tau protein is the main component of its pathogenesis. Calpain was found to be abnormally activated in neurofibrillary tangles (NFTs) in a previous report. Cornel iridoid glycosides (CIG) have been reported to reduce the hyperphosphorylation of tau protein. Nevertheless, the role of calpain in the reduction tau hyperphosphorylation by CIG remains unclear. In the present study, we investigated the effect of CIG on calpain activity through in vitro and in vivo experiments. Western blotting results suggested that CIG decreased the phosphorylation of tau at Ser 404 and Ser 262 sites in P301S mice. Moreover, CIG inhibited the activity of calpain and glycogen synthase kinase 3 (GSK-3) and enhanced the activity of protein phosphatase 2A (PP2A) both in vivo and in vitro. CIG also inhibited the activation of PP2A and reduced the GSK-3 activity caused by the calpain activator dibucaine. In addition, the main components of CIG, morroniside and loganin, play an equivalent role in reducing calpain activity, as the effect of their combined use is equivalent to that of CIG. The abovementioned findings revealed that CIG improved PP2A activity and reduced GSK-3 activity by adjusting the activity of calpain 1, leading to a reduction in the phosphorylation of tau. This study highlights the remarkable therapeutic potential of CIG for managing AD.
PubMed: 35096120
DOI: 10.1155/2022/9213046 -
Korean Journal of Family Medicine Sep 2019It has been reported that in 62.5% of cases of incurable cancer pain, the complaint is due to myofascial pain syndrome. Trigger point injections using dibucaine...
BACKGROUND
It has been reported that in 62.5% of cases of incurable cancer pain, the complaint is due to myofascial pain syndrome. Trigger point injections using dibucaine hydrochloride help patients with such cancer pain. This study evaluated the efficacy of trigger point injections for alleviating pain in patients with advanced cancer.
METHODS
Twenty patients with advanced cancer who had a life expectancy of 6 months or less and had been diagnosed with myofascial pain syndrome were treated with trigger point injections. Prior to treatment, a Visual Analog Scale (VAS) was used to measure the resting pain level and discomfort upon application of pressure on the site of pain. These values were compared with last treatment measurements.
RESULTS
The mean pre-treatment VAS scores for pain at rest and upon application of pressure on the pain site were 7.3 and 9.0, respectively. These scores decreased significantly to 1.95 and 3.2, respectively, after the treatment (P<0.05).
CONCLUSION
Trigger point injection is an alternative and effective pain control modality for advanced cancer patients with myofascial pain syndrome.
PubMed: 31487973
DOI: 10.4082/kjfm.18.0065 -
Evidence-based Complementary and... 2021Linn. (CQ) is a medicinal plant with good evidence for the treatment of hemorrhoids, listed in the Thai National List of Herbal Products in the oral dosage form. (Wall...
BACKGROUND
Linn. (CQ) is a medicinal plant with good evidence for the treatment of hemorrhoids, listed in the Thai National List of Herbal Products in the oral dosage form. (Wall ex. DC.) R. K. Jansen. (AP) is a medicinal plant with a local anesthetic effect.
OBJECTIVE
To investigate the potential of rectal suppositories containing CQ and AP extracts to alleviate symptoms of hemorrhoids compared with the commercialized rectal suppository containing hydrocortisone and cinchocaine.
MATERIALS AND METHODS
Hemorrhoid outpatients ( = 105) with different severity grades (I, II, or III) from eight hospitals in northern Thailand were included in this study. Hemorrhoid severity was graded by proctoscopy associated with either anal pain or bleeding related to hemorrhoids or both. The patients were randomly allocated to two groups: CQ-AP group ( = 52) or the commercialized rectal suppository group ( = 53). One suppository was rectally administered twice daily in the morning and at bedtime for seven days. Evaluations were performed by physicians on days 1, 4, and 8 of the study. The primary endpoints were bleeding and prolapse size, while the secondary endpoint was anal pain.
RESULTS
Baseline demographics, lifestyle, constipation, number of prolapses, grade of hemorrhoid severity, and duration of experiencing hemorrhoids were comparable in both groups of patients. The effects of CQ-AP and the commercialized rectal suppository on bleeding, prolapse size, and anal pain were comparable. The patients in both groups were satisfied with both products at comparable levels and stated a preference for further use in the case of hemorrhoids recurrence. In terms of safety, the patients in the commercialized rectal suppository group experienced a higher incidence of adverse events, including anal pain and bleeding.
CONCLUSION
Rectal suppositories containing a combined extract of CQ and AP show potential in alleviating hemorrhoidal symptoms with a good safety profile.
PubMed: 34765003
DOI: 10.1155/2021/5605323