The silkworm infection model has the potential to replace conventional animal models for evaluation of the efficacy and toxicity of investigational antifungal agents. Silkworms are relatively inexpensive, can be simply grown in large numbers and can be easily infected with pathogenic fungi, including mutant strains. Antifungal agents can then be injected into the silkworm either via the hemolymph to mimic intravenous administration or directly into the gut for oral administration, and their antifungal effect can be evaluated. Common features regarding the mechanisms of pharmacokinetics between the silkworm and mammals result in consistent therapeutic effectiveness of antifungal agents. ASP2397, a promising new antifungal agent, was discovered using the silkworm model. The conclusion is that silkworms can be a more ethical and less expensive alternative to standard animal models, particularly for the identification and testing of new antifungal agents.
Chinese prescription Kangen-karyu, comprised of six crude drugs, has received much attention due to its numerous biological activities. The present study reports therapeutic evidence for Kangen-karyu from pre-clinical animal experiments related to human diseases. Kangen-karyu showed beneficial effects on type 1 diabetes and related complications through the suppression of protein expression related to advanced glycation endproducts and oxidative stress. Kangen-karyu reduced oxidative stress via the regulation of dyslipidemia, and also exerted a renoprotective effect mainly through its antioxidant properties during the development of diabetic nephropathy in type 2 diabetes. In addition, Kangen-karyu showed neuroprotective effects by attenuating the spatial memory impairment and neuronal death induced by diabetes. Kangen-karyu counteracted oxidative stress and ameliorated tissue damage possibly associated with aging. These findings provide scientific evidence to explain the efficacy of Kangen-karyu based on its underlying therapeutic effects.
While exercise is widely believed to prevent atherothrombotic diseases, it occasionally causes sudden death. This exercise paradox may be due to the inadequate testing of the thrombotic and thrombolytic status. A recently developed shear-induced thrombosis/endogenous fibrinolysis test performed with non-anticoagulated blood samples allows the assessment of the thrombotic state of an individual both at rest and after exercise. This sensitive and physiologically relevant test may help to solve the aforementioned exercise paradox.
Whole transcriptome analyses have revealed a large number of novel long non-coding RNAs (lncRNAs). Although the importance of lncRNAs has been documented in previous reports, the biological and physiological functions of lncRNAs remain largely unknown. The role of lncRNAs seems an elusive problem. Here, I propose a clue to the identification of regulatory lncRNAs. The key point is RNA half-life. RNAs with a long half-life (t1/2 > 4 h) contain a significant proportion of ncRNAs, as well as mRNAs involved in housekeeping functions, whereas RNAs with a short half-life (t1/2 < 4 h) include known regulatory ncRNAs and regulatory mRNAs. This novel class of ncRNAs with a short half-life can be categorized as Short-Lived non-coding Transcripts (SLiTs). I consider that SLiTs are likely to be rich in functionally uncharacterized regulatory RNAs. This review describes recent progress in research into SLiTs.
We screened lactic acid bacteria that exhibited high innate immunity-stimulating activity by monitoring muscle contraction activity in silkworms. Heat-treated fractions of lactic acid bacteria, Leuconostoc carnosum #7-2, Leuconostoc gelidum #4-2, and Leuconostoc mesenteroides 8/11-3, had high (250-460 units/mg) innate immunity-stimulating activity. These lactic acid bacteria proliferated in milk to concentrations of 1 × 106 colony forming unit/mL. The present findings suggest that the silkworm muscle contraction assay is useful for screening lactic acid bacteria with high innate immunity-stimulating activity, and that the assay can be used for the production of fermented foods made from milk.
Leuconostoc carnosum #7-2, L. gelidum #4-2, and L. mesenteroides 8/11-3, which were isolated from fermented plant foods, are lactic acid bacteria. We previously reported that these bacteria are functional lactic acid bacteria whose innate immunity-stimulating activities are high based on a silkworm muscle contraction assay. The concentrations of these three lactic acid bacteria increased to more than 1 × 106 colony forming units (cfu)/mL in various vegetable and fruit juices when the pH values were appropriately adjusted. As the bacteria grew in the vegetable and fruit juices, the pH decreased and the concentrations of total sugars and glucose also decreased. These findings suggest that these functional lactic acid bacteria can be used to produce vegetable and fruit juices with reduced sugar levels, which is expected to be beneficial for human health.
This study was conducted in order to establish a health management method for the elderly in a community through follow-ups of bone mineral density (BMD) measurement results over a 1-year period based on BMD measurements performed by pharmacists and a guidance program. Regarding BMD measurement results, the percent young adult mean (%YAM: mean BMD in healthy persons of the same sex aged between 51 and 82 years old) significantly increased in Period I, during which the intervention by pharmacists was performed (6 months after the start of measurements), but significantly decreased in Period II, during which this intervention was not performed (between 7 and 12 months after the start of measurements). Based on these results, lifestyle improvements were effective in Period I regardless of sex or age; however, it may be important to maintain an improved diet and subject motivation in the future. The results of this study suggest that community pharmacists play an important role in community medicine through positive intervention for local residents' health support.
Aldose reductase (AR) has been the leading target in the treatment of diabetic cataract. Although numerous synthetic AR inhibitors (ARI) have been identified, their adverse side effects currently preclude their use. Olive leaf extract (OLE) as well as ginkgo leaf extract (GLE) are natural supplements that have wide therapeutic indices and a plethora of salutary effects during diabetes that so far untested on sugar cataract progression. As such, the present study sought to evaluate the AR-inhibiting properties of OLE and GLE using the isolated enzyme from rabbit lens. Biochemical analyses revealed that both OLE and GLE inhibited rabbit lens AR activity in a concentration-dependent manner with half maximal inhibitory concentration (IC50) 65 µg/mL and 72.5 µg/mL, respectively. Interestingly, the results of kinetic studies exhibited a differential pattern of inhibition by these two extracts. While an non-competitive inhibition of AR was promoted by OLE recognized by significant decrease in the apparent maximum velocity (Vmax) (0.12 ± 0.009677 µM/min versus 0.278 ± 0.0013677 µM/min) without significant change in Michaelis constant (Km), the GLE showed a competitive pattern of inhibition characterized by significant increase in apparent Km (4.4 ± 0.0068 µM), without change in Vmax value. It would appear that these classes of natural extracts represent effective and safe therapeutic options that hold the great promise for treatment not only diabetic cataract, but also other ocular diseases characterized by uncontrolled AR activity.
Rivaroxaban is an oral direct Factor Xa inhibitor approved in the European Union and the United Sates for the single-drug treatment of several thromboembolic diseases in adults. Ιt has been evaluated in large phase III clinical trials and has been found to have similar efficacy and safety with standard therapy. Herein, is described a very rare case of a rivaroxaban-induced spontaneous expanding chest wall hematoma, that required surgical intervention, in a breast cancer patient. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of hematoma and treatment with rivaroxaban. Physicians should be cautious when prescribing rivaroxaban in groups of patients associated with increased bleeding risk such as patients with impaired renal or hepatic function, hypertension, coronary heart disease, heart failure, patients with certain types of cancers and patients receiving concomitant medications which may alter the pharmacokinetic or pharmacodymamic parameters of rivaroxaban. Anticoagulant treatment should be tailored to each individual patient weighing the bleeding risk against the risk of recurrent thrombosis.
Abdominal cocoon, also termed sclerosing encapsulating peritonitis, is an uncommon entity associated with formation of a fibro-collagenous membrane around intestinal loops resulting in intestinal obstruction. Most reported cases are idiopathic, but many other causes have been implicated in cocoon formation, including use of continuous ambulatory peritoneal dialysis, peritoneal tuberculosis, and connective tissue disease. However, peritoneal carcinomatosis is a rarely reported entity that causes this condition. Reported here are two cases of abdominal cocoon secondary to peritoneal carcinomatosis. Both patients presented with intestinal obstruction; one underwent surgery but the other refused surgery.