Effect of aromatherapy on patients with Alzheimer's disease

Objective: Recently, the importance of non‐pharmacological therapies for dementia has come to the fore. In the present study, we examined the curative effects of aromatherpay in dementia in 28 elderly people, 17 of whom had Alzheimer's disease (AD). Methods: After a control period of 28 days, aromatherapy was performed over the following 28 days, with a wash out period of another 28 days. Aromatherapy consisted of the use of rosemary and lemon essential oils in the morning, and lavender and orange in the evening. To determine the effects of aromatherpay, patients were evaluated using the Japanese version of the Gottfries, Brane, Steen scale (GBSS‐J), Functional Assessment Staging of Alzheimer's disease (FAST), a revised version of Hasegawa's Dementia Scale (HDS‐R), and the Touch Panel‐type Dementia Assessment Scale (TDAS) four times: before the control period, after the control period, after aromatherpay, and after the washout period. Results: All patients showed significant improvement in personal orientation related to cognitive function on both the GBSS‐J and TDAS after therapy. In particular, patients with AD showed significant improvement in total TDAS scores. Result of routine laboratory tests showed no significant changes, suggesting that there were no side‐effects associated with the use of aromatherapy. Results from Zarit's score showed no significant changes, suggesting that caregivers had no effect on the improved patient scores seen in the other tests. Conclusions: In conclusion, we found aromatherapy an efficacious non‐pharmacological therapy for dementia. Aromatherapy may have some potential for improving cognitive function, especially in AD patients.     

Composite implantation of mesenchymal stem cells with endothelial progenitor cells enhances tissue-engineered bone formation

For successful tissue engineering, neovascularization of the implanted tissue is critical. Factors generated by endothelial cells are also considered crucial for the process of osteogenesis. The direct effects of supplementing tissue engineered constructs with cultured endothelial progenitor cells (EPCs) for enhancing bone regeneration have not been reported. In this study, we investigated the potential of EPCs to facilitate neovascularization in implants and evaluated their influence on bone regeneration. The influence of EPC soluble factors on osteogenic differentiation of mesenchymal stem cells (MSCs) was tested by adding EPC culture supernatant to MSC culture medium. To evaluate the influence of EPCs on MSC osteogenesis, canine MSCs-derived osteogenic cells and EPCs were seeded independently onto collagen fiber mesh scaffolds and co-transplanted to nude mice subcutaneously. Results from coimplant experiments were compared to implanted cells absent of EPCs 12 weeks after implantation. Factors from the culture supernatant of EPCs did not influence MSC differentiation. Coimplanted EPCs increased neovascularization and the capillary score was 1.6-fold higher as compared to the MSC only group (p < 0.05). Bone area was also greater in the MSC + EPC group (p < 0.05) and the bone thickness was 1.3-fold greater in the MSC + EPC group than the MSC only group (p < 0.05). These results suggest that soluble factors generated by EPCs may not facilitate the osteogenic differentiation of MSCs; however, newly formed vasculature may enhance regeneration of tissue-engineered bone.     

Increased expression of decorin during the regeneration stage of mdx mouse

Satellite cells exist in postnatal muscle tissue and constitute the main source of muscle precursor cells for growth and repair. These cells carry out important roles for skeletal muscle formation postnatally during growth of muscle mass as well as damage-induced regenerative processes. Muscle regeneration supports muscle function in aging and has a role in the functional impairment caused by progressive neuromuscular diseases. Major substances controlling this process are growth factors and extracellular matrix. Myostatin, a member of TGF-β family, was mainly expressed in muscle tissue. Decorin, a member of the small leucine-rich proteoglycan gene family, is composed of a core protein and a dermatan/chondroitin sulfate chain. Recent studies have shown that decorin enhanced the proliferation and differentiation of myogenic cells by suppressing myostatin activity. Thus, decorin appears to be a new molecule in the myostatin signaling pathway and a promising target for treatment of progressive neuromuscular diseases. Therefore, in this study, we examined the localization of decorin as well as myostatin in a muscular dystrophy model in mdx mice and B10 Scott Snells mice as a control to elucidate the differences between decorin and myostatin messages as well as protein distribution. This study revealed increased expression of decorin protein as well as mRNA at the regenerative stage of mdx mice compared to early stages, while only weak expression of decorin was detected in the control mice. Our study contributes to identifying the relationship between decorin and myostatin as well as the development of a therapeutic strategy for progressive neuromuscular diseases.     

Analysis of patients with advanced gastric cancer undergoing S-1/CDDP combined neoadjuvant chemotherapy

We retrospectively examined patients with advanced gastric cancer who underwent S-1/CDDP combined neoadjuvant chemotherapy. Nine patients who had the factor of curative surgery deemed not feasible for advanced gastric cancer were enrolled. 80 mg/m2 of S-1 was given orally from days 1-14, and 60 mg/m2 of CDDP was administered on day 8. Patients were treated with a three-cycle protocol. When an adverse event greater than Grade 3 showed, we judged that chemotherapy could not be continued and surgery was performed. An anti-tumor effect on the imaging was found in all cases of PR. The histological effect was judged to be Grade 3 and pathological CR in two cases. In the postoperative period, all patients received adjuvant chemotherapy. S-1/CDDP combined neoadjuvant chemotherapy is a potential regimen for advanced gastric cancer.     

Early diagnosis of metastatic spinal tumor is a key for effective palliative radiotherapy in patients with lung cancer

Patients with metastatic spinal tumor are the largest in number among the patients with bone tumor. It causes a severe bone pain, pathological fracture and spinal cord compression. Thus it harshly hampers patient's quality of life. We report 3 patients with lung cancer whose initial manifestation was metastatic spinal tumor. We treated the 3 patients with palliative radiotherapy and medication. Although the severe pain has improved on a numerical rating scale(NRS), but performance status(PS)and activity of daily living(ADL)of the 3 patients got worse because the disease was progressed and complicated. Generally, PS of cancer patients found by bone matastasis is low. However, it is difficult to take an effective treatment, which leads to ADL improvement. There are many choices for treating metastatic bone tumors including pain control, bisphosphonate administration, radiation therapy, strontium radiotherapy, bone cement, palliative surgery and orthotics. In addition, a development of molecular target drugs, such as Denosmab, is expected as future modality of palliative care. In conclusion, we should detect a bone metastasis in the patient with lung cancer as early as possible, and select an appropriate treatment in collaboration with each specialist for achieving the ADL and PS improvement.     

A protective role of hydrogen sulfide against oxidative stress in rat gastric mucosal epithelium

We investigated effect of hydrogen sulfide (H(2)S) on oxidative stress-caused cell death in gastric mucosal epithelial cells. In rat normal gastric epithelial RGM1 cells, NaHS, a H(2)S donor, at 1.5mM strongly suppressed hydrogen peroxide (H(2)O(2))-caused cell death, while it slightly augmented the H(2)O(2) toxicity at 0.5-1mM. The protective effect of NaHS was abolished by inhibitors of MEK or JNK, but not of p38 MAP kinase. NaHS at 1.5mM actually phosphorylated ERK and JNK in RGM1 cells. Glibenclamide, an ATP-sensitive K(+) (K(ATP)(+)) channel inhibitor, did not affect the protective effect of NaHS, although mRNAs for K(ATP)(+) channel subunits, Kir6.1 and SUR1, were detected in RGM1 cells. In anesthetized rats, oral administration of NaHS protected against gastric mucosal lesion caused by ischemia-reperfusion. These results suggest that NaHS/H(2)S may protect gastric mucosal epithelial cells against oxidative stress through stimulation of MAP kinase pathways, a therapeutic dose range being very narrow.     

N-terminus of Etanercept is Proteolytically Processed by Dipeptidyl Peptidase-4

Pharmaceutical Research - Biologics are structurally heterogeneous and can undergo biotransformation in the body. Etanercept (ETN) is a fusion protein composed of a soluble tumor necrosis factor...     

A 56 Year-Old Female with Congenital Hepatic Fibrosis Diagnosed by Laparoscopy

Abstract: We describe a 56-year-old woman with congenital hepatic fibrosis. Blood tests and liver scanning with Tc-99m-labelled galactosyl human serum albumin revealed mild liver dysfunction. Per-rectal portal scintigraphy with iodine-123 iodoamphetamine showed severe abnormalities in the portal circulation, and the portal pressure measured during percutaneous transhepatic portography was high (350 mmH₂O). Idiopathic portal hypertension was suspected. Laparoscopy disclosed diffuse, intense dendritic white markings around the liver. Congenital hepatic fibrosis was confirmed on histologic examination of a biopsy specimen obtained during laparoscopy. In summary, we report a rare and relatively elderly case of CHF, in which laparoscopy was useful in the diagnosis. (Dig Endosc 1999; 11: 174–178)     

Clinical efficacy and safety of second line and salvage aflibercept for advanced colorectal cancer in Akita prefecture

BACKGROUNDAngiogenesis inhibitors (AIs) combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer (CRC). Aflibercept (AFL) is an option for second-line treatment of CRC, according to the ‘VELOUR’ trial. Currently, we can choose from three AIs, including bevacizumab, ramucirumab, and AFL. Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action. We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment.AIMTo determine and compare the efficacy and safety profiles of AFL in the second-line and salvage therapy settings.METHODSClinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan (FOLFIRI) regimen were collected retrospectively from six institutions in Japan, for the period from May 2017 to March 2019. Patient characteristics collected included age, sex, tumor location, RAS and RAF status, metastatic sites, number of previous treatment cycles, therapeutic response, adverse events, duration of previous AI treatment, and survival time. The end points were time to AFL treatment failure (aTTF) and median survival time post-AFL (aMST). Statistical analyses were performed to compare the efficacy and safety in the second-line setting with those of the salvage therapy setting, which was defined as the days since the end of second-line therapy. RESULTSAll 41 patients who received AFL + FOLFIRI for advanced CRC had metastatic or unresectable cancer. Twenty-two patients received AFL in the second-line setting and nineteen in the salvage therapy setting. The patient characteristics were similar in the two groups, except for two factors. The median duration of the previous AI administration was shorter in the second-line patients compared with that in the salvage therapy patients (144 d vs 323 d, P = 0.006). In the second-line and salvage therapy groups, the objective response rates were 11% and 0%, respectively (P = 0.50), and the disease control rates were 53% and 50%, respectively (P = 1.00). In the second-line and salvage therapy groups, the aTTF (123 d vs 71 d, respectively), aMST (673 d vs 396 d, respectively), and incidence of adverse events of grade 3 [8 (36%) vs 9 (47%)] were not significantly different between the two groups.CONCLUSIONAFL can be used to treat advanced CRC patients, with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.