Traditional Chinese and Japanese medicines have become prime sources of drug discovery and there is a pressing need to investigate the effectiveness of these traditional medicines for modern drug discovery. Recently, among various traditional formulations, studies on Kangen-karyu (Guan-Yuan-Ke-Li), a mixture of six medicinal herbs (Salviae Miltiorrhizae Radix, Cnidii Rhizoma, Paeoniae Radix, Carthami Flos, Aucklandiae Radix, and Cyperi Rhizoma), have been growing to assess its neuroprotective role. This prompted us to undertake a thorough review of various targets of Kangen-karyu regarding its effectiveness against Alzheimer's disease, particularly focusing on cholinesterases, beta-site amyloid precursor protein cleaving enzyme 1, and glycogen synthase kinase 3β. This review provides new insights into Kangen-karyu medication as a prospective anti-Alzheimer's medication and indicates the need for in-depth in vivo investigation in the future.
The virus severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is currently affecting more than 200 countries and territories worldwide. It has been declared as pandemic by World Health Organization (WHO) and the whole world is suffering from corona virus disease 2019 (COVID-19). Currently, no treatment for SARS-CoV-2 are approved because of lack of evidence, but a number of clinical trials are in process and we are expecting fruitful results very soon. This review focuses on various approaches of treatment and few of the most recent clinical trials carried out in this field.
The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification.
Tacrolimus, a calcineurin inhibitor, affects bone metabolism and increases the risk of fracture due to marked bone loss. Bisphosphonates increase the bone mineral density (BMD) in osteoporosis patients. Menatetrenone has less positive effects on BMD but reduces the risk of fracture by improving bone quality. In this study, we investigated the effectiveness of the combined administration of risedronate and menatetrenone against bone loss induced by tacrolimus. Wistar rats were divided into four groups:  control,  tacrolimus at 1.5 mg/kg,  tacrolimus + risedronate at 1.0 mg/kg, and  tacrolimus + risedronate + menatetrenone at 20 mg/kg. After the drugs were administered for 4 weeks, bone histomorphometric analysis was performed and bone strength was evaluated using a three point bending method. BMD was measured using quantitative computed tomography. Tacrolimus significantly reduced the BMD and strength properties of the lower limb bones. These tacrolimusinduced decreases were suppressed by risedronate treatment. The combined administration of risedronate and menatetrenone more significantly improved bone strength properties than risedronate alone. Bone histomorphometric analysis revealed a significant increase in bone resorption with tacrolimus. Risedronate alone significantly suppressed the tacrolimus-induced increase in bone resorption but simultaneously reduced bone formation. On the other hand, the combined administration of risedronate and menatetrenone suppressed the tacrolimus-induced increase in bone resorption, in addition to the significant risedronate-induced decrease in bone formation. This study suggests that the combined administration of risedronate and menatetrenone improves bone strength in tacrolimus-treated rats by preventing and ameliorating the risedronate-induced suppression of bone formation.
Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. A number of new therapies have been developed based on the pathogenic factors of diabetic nephropathy such as intensive glycemic control, precise hypertension control, lifestyle modifications including exercise and an energy-restricted diet, and numerous novel agents. The utilization of traditional Chinese medicine for patients with diabetic nephropathy has also received increasing attention due to its wide availability, weak side-effects, and proven therapeutic mechanisms and benefits. In this paper, we report the case of patients with diabetic nephropathy, stage 2 or 3. Kangen-karyu extract (7.5 g/day) was administered three times per day for 6 months. The estimated glomerular filtration rate was increased at the 6-month follow-up. The serum creatinine level decreased following administration. At that time, somatic and subjective symptoms had partially disappeared. Here, we present evidence that Kangen-karyu exerts a renoprotective effect against the development of diabetic nephropathy.
Infantile hemangioma is a benign cutaneous tumor, which sometimes rapidly enlarges, causes cosmetic problem, destroys normal tissue, and possibly threatens life. Dye lasers, steroid administration, and watchful waiting had been the treatment options for infantile hemangioma, but in recent years propranolol therapy has become available. The mechanism underlying the action of propranolol, however, is still unknown. We hypothesized that cytokines whose expressions change before and during the treatment are responsible for the efficacy of the drug. This study aims to prove the hypothesis using patients' sera and membrane array. In this study, the serum cytokine concentrations of five patients with infantile hemangioma were measured using membrane array of 20 angiogenic cytokines. We compared them before and during propranolol treatment to identify the cytokines responsible for the effect of propranolol. Signals for angiogenin, epidermal growth factor (EGF), platelet-derived growth factor-BB (PDGF-BB), regulated on activation, normal T-cell expressed and secreted chemokine (RANTES), tissue inhibitor of metalloproteinases 1 (TIMP-1), and tissue inhibitor of metalloproteinases 2 (TIMP-2) were evident in all five cases before treatment. Furthermore, PDGF-BB was the only cytokine of which concentration was decreased during treatment with statistically significant difference. This report is a pilot study with a small number of samples, and further detailed research with increased number of samples is necessary. Nonetheless, our results suggest that PDGF-BB may be involved in the action of propranolol. In addition, its serum concentration can be utilized as a potential marker of the therapeutic effect.
The management of patients with brain abscess poses a significant challenge to clinicians in patients with chronic kidney disease. Obtaining a biopsy sample from the affected area is the mainstay in the diagnosis, but it is often unavailable. In most cases, therapy is guided by clinical findings and imaging alone. We discuss three cases of brain abscess- each with a different scenario and discuss the issues faced in management. The first case was a 32-year-old post-renal transplant male patient with a brain abscess due to dematiaceous fungi and was treated with amphotericin. The second case was a 42-year-old female patient with stage 5 chronic kidney disease on maintenance hemodialysis who presented with a brain abscess due to suspected fungal infection based on imaging findings and was managed with antibiotics and voriconazole. The third case was a 42-year-old post-renal transplant male patient who presented with a brain abscess due to nocardiosis and was managed with cotrimoxazole, meropenem and linezolid. We also summarize the approach to the management of brain abscess in resource-limited settings.
The authors present the use of prostaglandin E1 (PGE1) for the treatment of an acute paracentral acute middle maculopathy (PAMM). A 78-year-old white female was seen with a sudden loss of vision in her left eye (OS) to 20/200 noted upon awakening. The right eye (OD) saw 20/20. A complete eye exam was done and an ocular coherent tomography revealed retinal thickening and a whitening of the inner nuclear layer in the area of the macula OS. A diagnosis of PAMM in the OS was made. Treatment was immediately started with 70 μg of PGE1 administered over 1.5 hours in the form of a skin cream. A volume of 3.5 cc of skin cream was applied in divided doses to the inner surface of the forearm, rubbed into the skin and allowed to dry. The same 70 μg of PGE1 in 3.5 cc of skin cream was repeated once the next morning. The patient began to see better the second day of treatment with a final visual acuity of 20/20. The OD was unchanged. After 14 months she was stable with no further treatment. PAMM is an ischemic process of the inner retina. PGE1, a potent vasodilator of the microcirculation, when given immediately seemed to be useful in restoring vision in this form of retinal ischemia. Treatment was immediately started with PGE1 in the form of a skin cream with visual improvement. The authors normally use PGE1 intravenously for acute ocular ischemia and would have preferred that here. Intravenous PGE1 was not available and was substituted with the skin cream of PGE1 that worked well for the patient.
The world is in the midst of the coronavirus disease 2019 (COVID-19) pandemic. Interleukin 6 (IL-6) inhibitor (tocilizumab) had been suggested for the treatment of acute respiratory distress syndrome (ARDS) patients based on the concept of "cytokine storm" in COVID-19. However, we still lack reliable studies to verify "cytokine storm" in COVID-19 pneumonia. Furthermore, IL-6 inhibitor has potential hazards of inducing infectious diseases. The efficacy of IL-6 monoclonal antibody-directed therapy remains to be fully evaluated.
Drug quantity purchase in China has reshaped the pattern of drug market with lower price of generic drugs and relatively higher price of original brand-name drugs. However, most Chinese people do not trust the safety and efficacy of the generic drugs that sold at a very low price. Ultra-low price of generic agents may weaken patients' drug recognition and compliance, and affect the implementation of drug quantity purchase policy.
Based on some publications that associate SARS-CoV-2 infection with the use of anti-hypertensive drug groups such as angiotensin-converting-enzyme inhibitors (e.g. enalapril) or angiotensin II receptor blockers (e.g. losartan), many patients from South America, Central America or Spain, have stopped or intend to interrupt their treatments with these drugs. Hence, it may exist ominous consequences due to this drop out. For this reason, it is necessary to quickly warn about this situation and the risks associated with it.
The recent clinical trial reports pertaining to the efficacy of chloroquine and hydroxychloroquine against COVID-19 albeit yet to be validated with larger clinical trials, have sparked much interest globally to evaluate whether this anti-malarial drug can be repurposed for the treatment of COVID-19. In addition to its anti-viral activity, the anti-inflammatory activity of chloroquine may also contribute to its efficacy. Based on our data obtained from an animal infection model of melioidosis (a disease caused by the bacteria Burkholderia pseudomallei), treatment with chloroquine can result in the phosphorylation and consequent inhibition of glycogen synthase kinase-3β (GSK3β). This serine/threonine protein kinase is now recognised as a point of convergence for host inflammatory response. In view of this, it is plausible that the mechanism for the anti-inflammatory effect of chloroquine against COVID-19 involves inhibition of host GSK3β.