Motor discoordination of transgenic mice overexpressing a microtubule destabilizer, stathmin, specifically in Purkinje cells

The proper regulation of microtubule (MT) structure is important for dendritic and neural circuit development. However, the relationship between the regulation of the MTs in dendrites and the formation of neural function is still unclear. Stathmin is a MT destabilizer, and we have previously reported that the expression and the activity of stathmin is downregulated during cerebellar Purkinje cell (PC) development. In this study, we generated transgenic mice that specifically overexpress the constitutively active form of stathmin in the PCs. These mutant mice did not show any obvious morphological or excitatory transmission abnormalities in the cerebellum. In contrast, we observed a decline in the expression of MAP2 and KIF5 signal in the PC dendrites and a discoordination of motor function in the mutant mice, although they displayed normal general behavior. These data indicate that the overexpression of stathmin disrupts dendritic MT organization, motor protein distribution, and neural function in PCs.     

Incidence rate of injection-site granulomas resulting from the administration of luteinizing hormone-releasing hormone analogues for the treatment of prostatic cancer

PURPOSE: Granulomas resulting from the administration of luteinizing hormone-releasing hormone analogues (LH-RH analogues) are thought to be very rare. We report on our clinical experience with injection-site granulomas that result from the administration of LH-RH analogues, and we evaluate the incidence rate of these granulomas. MATERIALS AND METHODS: We used the clinical records of 118 patients who were administered LH-RH analogues in 2005. We describe the clinical data of patients who experienced injection-site granulomas and evaluated the incidence rate. RESULTS: Five patients demonstrated injection-site granulomas due to LH-RH analogue administration. The incidence rate was 4.2% (5 of 118 patients). Most of the granulomas occurred after the first or second administration of 11.25mg of leuprorelin acetate. CONCLUSION: The occurrence of granulomas resulting from the administration of LH-RH analogues was thought to be very rare. Our study, however, revealed a higher incidence rate than expected, especially for leuprorelin acetate.     

Preoperative change of modified Glasgow prognostic score after stenting predicts the long-term outcomes of obstructive colorectal cancer

Inflammation-based markers predict the long-term outcomes of various malignancies. We investigated the relationship between the modified Glasgow prognostic score (mGPS) and the long-term outcomes of obstructive colorectal cancer in patients who underwent self-expandable metallic colonic stent placement and subsequently received curative surgery. We retrospectively analyzed 63 consecutive patients with pathological stage II and III obstructive colorectal cancer from 2013 to 2018. The mGPS was calculated before stenting and surgery, and the difference of the scores was defined as the d-mGPS. All d-mGPS = 2 patients were > 70 years of age (p = 0.01). Postoperative complications were more common in the preoperative mGPS = 2 group (p = 0.02). The postoperative hospital stay was significantly longer in the mGPS = 2 group (p = 0.007). Multivariate analyses revealed that d-mGPS was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] = 9.18, p = 0.004) and cancer-specific survival (HR = 9.98, p = 0.01). Preoperative mGPS = 2 was significantly associated with poor OS (HR = 5.53, p = 0.04). The results indicated that mGPS might serve as a valuable indicator of the immunonutritional status of preoperative patients, and a preoperative change of the status might affect the long-term outcomes of patients with obstructive colorectal cancer.     

Transsphenoidal cyst cisternostomy with a keyhole dural opening for sellar arachnoid cysts: technical note

A less invasive transsphenoidal approach with a keyhole dural opening for intrasellar arachnoid cysts is described. This approach was used to address seven sellar cystic lesions with suprasellar extension; they were six intrasellar arachnoid cysts (IACs) and one Rathke’s cleft cyst (RCC). In all cases, preoperative MRI revealed cerebrospinal fluid (CSF) intensity on both T1- and T2-weighted images. On preoperative contrast-enhanced MRI, five of the six IACs manifested posterior displacement of the flattened pituitary gland toward the dorsum sellae; one of the six IACs and the RCC exhibited a flattened pituitary gland on the anterior surface of the cyst. Wide cyst cisternostomy through a keyhole dural opening was carried out safely using a microscope with the support of a thin angled endoscope (30° and/or 70°, diameter 2.7 mm). As we aimed to avoid iatrogenic injury of the pituitary function, we found it difficult to obtain a sufficiently wide and precise opening of the cyst wall when the pituitary gland was located on the anterior surface of the cyst wall. Our approach facilitates safe cyst cisternostomy as wide as that obtainable by transcranial manipulation. In addition, CSF leakage is prevented by dural plasty using the fascia lata and stitching with 6-0 monofilament sutures. This technique can be adapted to address various sellar cystic lesions. However, as the posterior or anterior displacement of the normal pituitary gland in the presence of IACs or RCCs, respectively, affects the width of the cyst opening, our technique is more suitable for IACs than RCCs.     

Reduced Frontal Glutamate + Glutamine and N-Acetylaspartate Levels in Patients With Chronic Schizophrenia but not in Those at Clinical High Risk for Psychosis or With First-Episode Schizophrenia

Changes in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy (¹H MRS) studies at each clinical stage of schizophrenia indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic metabolites change progressively. However, to our knowledge, no single study has addressed the possible differences in ¹H MRS abnormalities in subjects at 3 different stages of disease, including those at ultrahigh risk for psychosis (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia (ChSz). In the current study, 24 patients with UHR, 19 FES, 25 ChSz, and their demographically matched 3 independent control groups (n = 26/19/28 for the UHR, FES, and ChSz control groups, respectively) underwent ¹H MRS in a 3-Tesla scanner to examine metabolites in medial prefrontal cortex. The analysis revealed significant decreases in the medial prefrontal NAA and glutamate + glutamine (Glx) levels, specifically in the ChSz group as indexed by a significant interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls) (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with the other metabolites in the patients with ChSz was also supported by a significant interaction between the clinical status and types of metabolites that only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present study demonstrates significant differences in ¹H MRS abnormalities at different stages of schizophrenia, which potentially correspond to changes in glutamatergic neurotransmission, plasticity, and/or excitotoxicity and regional neuronal integrity with relevance for the progression of schizophrenia.Key words: anterior cingulate cortex, at-risk mental state, biomarkers, frontal lobe, magnetic resonance imaging, neurochemical abnormality     

Significance of combined cyclosporine−prednisolone therapy and cyclosporine blood concentration monitoring for idiopathic membranous nephropathy with steroid-resistant nephrotic syndrome: a randomized controlled multicenter trial

Background

Combined treatment with cyclosporine microemulsion preconcentrate (CyA MEPC) and steroids has been widely used for idiopathic membranous nephropathy (IMN) associated with steroid-resistant nephrotic syndrome (SRNS). Recent studies have shown that once-a-day and preprandial administration of CyA MEPC is more advantageous than the conventional twice-a-day administration in achieving the target blood CyA concentration at 2 h post dose (C2). We designed a randomized trial to compare these administrations.

Methods

IMN patients with SRNS (age 16–75 years) were divided prospectively and randomly into 2 groups. In group 1 (n = 23), 2–3 mg/kg body weight (BW) CyA MEPC was given orally once a day before breakfast. In group 2 (n = 25), 1.5 mg/kg BW CyA MEPC was given twice a day before meals. CyA + prednisolone was continued for 48 weeks.

Results

Group 1 showed a significantly higher cumulative complete remission (CR) rate (p = 0.0282), but not when incomplete remission 1 (ICR1; urine protein 0.3–1.0 g/day) was added (p = 0.314). Because a C2 of 600 ng/mL was determined as the best cut-off point, groups 1 and 2 were further divided into subgroups A (C2 ≥600 ng/mL) and B (C2 <600 ng/mL). Groups 1A and 2A revealed significantly higher cumulative remission (CR + ICR1) (p = 0.0069) and CR-alone (p = 0.0028) rates. On the other hand, 3 patients with high CyA levels (C2 >900 ng/mL) in Group 1A were withdrawn from the study because of complications.

Conclusion

CyA + prednisolone treatment is effective for IMN with associated SRNS at a C2 of ≥600 ng/mL. To achieve remission, preprandial once-a-day administration of CyA at 2–3 mg/kg BW may be the most appropriate option. However, we should adjust the dosage of CyA by therapeutic drug monitoring to avoid complications.     

Low-Volume Walking Program Improves Cardiovascular-Related Health in Older Adults

Although numerous sources of evidence show that regular physical activity is beneficial to health, most individuals do not engage in a sufficient amount of physical activity to meet the guidelines set out by expert panels. In addition, the minimum amount of physical activity associated with reduced cardiovascular disease risk markers is not clear in older adults. The purpose of this study was to determine the effects of a 12-week walking program involving an exercise volume below the current minimum physical activity recommendation on cardiovascular disease risk markers in older adults. The participants were recruited from the following two groups separately: a walking group (n = 14) and a control group (n = 14). In the walking group, participants walked 30 to 60 minutes per session on 2 days per week for 12 weeks (average walking time, 49.4 ± 8.8 min/session). Plasma oxidised low-density lipoprotein concentrations tended to be lower than baseline values in the walking group after 12 weeks (paired t-test, p = 0.127). The ratio of oxidised low-density lipoprotein to high-density lipoprotein cholesterol was significantly lower than the baseline ratio in the walking group after 12 weeks (paired t-test, p = 0.035). Resting systolic blood pressure and diastolic blood pressure were significantly lower than baseline values in the walking group after 12 weeks (paired t-tests, p = 0.002, p < 0.0005, respectively). Our findings demonstrate that a 12-week walking program comprising a low volume of physical activity confers a benefit to cardiovascular-related health in older adults.

Key Points

• It is important to consider baseline physical activity levels when evaluating physical activity program.
• Being physically active is important to reduce the potential risk marker of cardiovascular disease in older adults.
• These data imply that a small volume of 12-week walking program confers a benefit to cardiovascular-related health in older adults.

Key words: blood pressure, exercise, lipid metabolism, older adults, oxidised low-density lipoprotein