[Clinical features and prognostic factors of elderly patients with mantle cell lymphoma].

Objective: To examine the clinical characteristics and prognostic factors of elderly patients with mantle cell lymphoma (MCL) and the impact of nutrition and underlying diseases on the prognosis of elderly patients with MCL. Methods: retrospectively analyzed 255 elderly patients with MCL from 11 medical centers, including Peking University Third Hospital between January 2000 and February 2021. We analyzed clinical data, such as age, gender, Mantle Cell Lymphoma International Prognostic Index score, and treatment options, and performed univariate and multivariate prognostic analysis. We performed a comprehensive geriatric assessment on elderly MCL patients with medical records that included retraceable underlying disease and albumin levels, and we investigated the impact of basic nutrition and underlying disorders on MCL prognosis in the elderly. Results: There were 255 senior individuals among the 795 MCL patients. Elderly MCL was more common in males (78.4%), with a median age of 69 yr (ages 65-88), and the majority (88.6%) were identified at a late stage. The 3-yr overall survival (OS) rate was 42.0%, with a 21.2% progression-free survival (PFS) rate. The overall response rate (ORR) was 77.3%, with a 33.3% total remission rate. Elderly patients were more likely than younger patients to have persistent underlying illnesses, such as hypertension. Multivariate analysis revealed that variables related with poor PFS included age of ≥80 (P=0.021), Ann Arbor stage Ⅲ-Ⅳ (P=0.003), high LDH level (P=0.003), involvement of bone marrow (P=0.014). Age of ≥80 (P=0.001) and a high LDH level (P=0.003) were risk factors for OS. The complete geriatric assessment revealed that renal deficiency was associated with poorer OS (P=0.047) . Conclusions: Elderly MCL patients had greater comorbidities. Age, LDH, renal function, bone marrow involvement, and Ann Arbor stage are all independent risk factors for MCL in the elderly.

[Development of a Ranking Tool for Scientificity, Transparency and Applicability of Clinical Practice Guidelines].

Objective: To address the limitations of existing methods and tools for evaluating clinical practice guidelines, we aimed to develop a comprehensive instrument focusing on the three main dimensions of guideline development: scientificity, transparency, applicability. We will use it to rank the guidelines according to the scores. We abbreviated it as STAR, and its reliability, validity and usability were also tested. Methods: A multidisciplinary expert working group was set up, including methodologists, statisticians, journal editors, medical professionals, and others. Scoping review, Delphi methods and hierarchical analysis were used to determine the final checklist of STAR. Results: The new instrument contained 11 domains and 39 items. Intrinsic reliability of each domain was indicated by Cronbach's α coefficient, with a average value of 0.646. The Cohen's kappa coefficients for methodological evaluators and clinical evaluators were 0.783 and 0.618. The overall content validity index was 0.905. The R2 for the criterion validity analysis was 0.76. The average score for usability of the items was 4.6, and the mean time spent to evaluate each guideline was 20 minutes. Conclusion: The instrument has good reliability, validity and evaluating efficiency, and can be used for evaluating and ranking guidelines more comprehensively.

[Clinical research on posterior single-implant occlusal contact time and force changes].

Objective: To investigate the changes of occlusal delay time, percentage of occlusal force and patients' subjective satisfaction of masticatory function for single implant crown in one year after the application of space reserved occlusion design. To provide data support and suggestions for clinical occlusion design. Methods: Patients who had received single posterior dental implant restoration in Department of Prosthodontics, Capital Medical University School of Stomatology from January 2019 to December 2019 were selected. At 0.5, 3, 6 and 12 months after restoration, the T-scan Ⅲ occlusal analyzer was used to detect and record the initial occlusal contact time of the natural tooth and implanted single crown, the occlusal force percentage of single implant prosthesis and corresponding tooth on the contralateral side (control teeth) on the contralateral side (control teeth) were also recorded. Subjective satisfaction with the masticatory function of the implants was recorded using visual analogue scale (VAS). The changes of occlusal delay time (the difference of the initial occlusal time between implant restoration and the natural teeth), percentage of occlusal force and patients' subjective feeling with time were analyzed. All data were analyzed by repeated measurement analysis of variance, bilatteral P<0.01 was considered statistically significant. Results: A total of 48 patients aged (36.8±8.4) years (23 males, 25 females, aged 23-50 years) were recruited. The occlusal delay time at 0.5 months was 0.15 (0.08, 0.20) s, at 3 months was 0.11 (0.06, 0.16) s, at 6 months was 0.07 (0.03, 0.13) s and at 12 months was 0.06 (0.03, 0.10) s. The occlusal delay time was shortened at every two time points, and the occlusal force percentage of the implant crown increased significantly. The percentage of occlusal force of implant prosthesis at 0.5 months was (7.7±4.8)%, at 3 months was (10.6±5.9)%, at 6 months was (12.3±6.2)% and at 12 months was (13.2±6.7)%. The most significant change was during the period of 0.5-3 months. At 0.5 months, the occlusal force of implant prosthesis was significantly lower than that of control teeth (14.3±6.5)% (P<0.01). The VAS score at 0.5 months was (7.06±1.64) and was (8.71±0.74) at 12 months. The score was increased and the difference was statistically significant from 3 month to 12 month (P<0.01). Conclusions: The change of occlusal force percentage of single posterior dental implant is most obvious within 3 months after restoration. The occlusal condition should be reexamined and adjust occlusal after 3 months of implant restoration as appropriate.

Effects of feeding corn bran and soybean hulls on nutrient digestibility, rumen microbial protein synthesis, and growth performance of finishing lambs.

Some grain processing by-products rich in digestible fiber are good feed resources for ruminants. This experiment was conducted to investigate the effects of replacing a portion of corn and corn stover with the combinations of corn bran and soybean hulls in the diet of fattening lambs on nutrient digestion, rumen microbial protein synthesis, and growth performance. A total of 36 Dorper × Small Thin-Tailed crossbred ram lambs (BW = 22.2 ±â€¯0.92 kg; mean ±â€¯SD) were randomly divided into three groups, and each group was fed 1 of 3 treatment diets: 1) 0% corn bran and soybean hulls (control); 2) 9% corn bran and 9% soybean hulls (18MIX); and 3) 17% corn bran and 17% soybean hulls (34MIX). The feeding experiment was conducted for 70 days, with the first 10 days for adaption. The DM intake was higher for 34MIX (1635.3 g/d) than for control diet (1434.7 g/d; P = 0.001). Lambs fed 18MIX and 34MIX diets (230.2 and 263.6 g/d, respectively) had higher average daily gain and feed efficiency than those fed control diet (194.8 g/d; P < 0.01). Dry matter and NDF digestibility for 34MIX group (60.9 and 49.5%) were higher than for control (55.2 and 41.3%; P < 0.01). No difference was observed in nitrogen digestibility among treatment diets (P = 0.778). The lambs fed 34MIX diet excreted more urinary purine derivatives, indicating that more microbial protein was yielded than those fed control diet (P < 0.01), while 18MIX was not different from the other two diets (P > 0.05). The metabolizable protein supplies were improved with increasing co-products inclusion rate. The results indicated that corn bran and soybean hulls in combination can effectively replace a portion of corn and corn stover in the ration of finishing lambs with positive effect on nutrient digestion and growth performance.

Extracorporeal shock wave therapy (ESWT) may be helpful in the osseointegration of dental implants: A hypothesis.

In recent decades, with the rapid development of dental implant technology, dental implants have been widely used in clinical practice. Various complications, including a lack of osseointegration, may occur after dental implantation. However, the occurrence of osteointegration failure after dental implantation is often complicated and unpredictable, and existing treatment methods cannot reverse osteointegration failure to achieve the optimum condition. A noninvasive, easy-to-operate, low-cost, fast-acting mechanotherapy is expected to solve this problem. Extracorporeal shock wave therapy (ESWT) is widely used to treat delayed healing, bone nonunion fractures, femoral head necrosis and other orthopedic diseases and plays a significant role in promoting bone regeneration. Studies have shown that ESWT can promote bone formation and osseointegration of titanium devices in vivo. In previous experiments, ESWT was found to regulate the activity of inflammatory cells, osteoblasts and mesenchymal stem cells. Studies have also mentioned the role of ESWT in promoting angiogenesis and bactericidal activity. Therefore, our hypothesis is that extracorporeal shock wave therapy can facilitate the realization of osteointegration by regulating the immune response, inducing regeneration of the jaw and alveolar bone, and promoting angiogenesis and bactericidal efficacy.

Reduced long non-coding RNA PTENP1 contributed to proliferation and invasion via miR-19b/MTUS1 axis in patients with cervical cancer.

OBJECTIVE: Many studies showed that long non-coding RNAs (lncRNAs) may serve as prospective markers for patients with malignant cancers, including cervical cancer (CC). In this study, we mainly investigate the functions of lncRNA PTENP1 in the progression of human CC. MATERIALS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to detect expression levels of PTENP1, miR-19b and MTUS1 in CC tissues, the adjacent tissues and CC cell lines. The correlations between PTENP1 with miR-19b, miR-19b with MTUS1 and PTENP1 with MTUS1 were analyzed. Overall survival (OS) of patients was analyzed using Kaplan-Meier method. Proliferation capacity was measured by CCK-8 assay and the invasion ability in CC cell line was detected by transwell assay. Western blot (WB) assay was performed to measure protein levels of tissues and CC cell lines. Finally, Dual-Luciferase reporter assay was performed to prove the potential binding sites between PTENP1 and miR-19b, miR-19b and MTUS1. RESULTS: We found that PTENP1 was reduced in CC tissues and CC cell lines, which predicted the poor diagnosis of CC patients. MiR-19b was increased in CC tissues, which was negatively correlated with PTENP1 in CC tissues. MTUS1 was reduced in CC tissues, which was negatively correlated with miR-19b and positively correlated within PTENP1 CC tissues. Furthermore, PTENP1 overexpression inhibited cell proliferation ability and invasion capacity in HeLa cells, as well as repressed expressions of Cyclin D1, N-cadherin, and Vimentin. Moreover, Luciferase gene reporter assays verified that miR-19b was a direct target miRNA of PTENP1, and MTUS1 was identified as a direct target of miR-19b. In addition, the inhibited cell proliferation and invasion abilities in HeLa cells with p-PTENP1 were eliminated following with miR-19b mimic transfection. CONCLUSIONS: According to the results, this study showed that PTENP1 was reduced in CC patients and it was a prognostic factor for CC patients. Furthermore, we firstly uncovered that PTENP1 could inhibit cell proliferation and invasion via miR-19b/MTUS1 in CC patients, which uncovered the tumor-suppressive role of PTENP1 in CC and suggested that it might be a potential target for treating human CC.

Replacing soybean meal with flax seed meal: effects on nutrient digestibility, rumen microbial protein synthesis and growth performance in sheep.

Flax seed meal (FSM) is rich in various nutrients, especially CP and energy, and can be used as animal protein feed. In animal husbandry production, it is a long-term goal to replace soybean meal (SBM) in animal feed with other plant protein feed. However, studies on the effects of replacing SBM with FSM in fattening sheep are limited. The aim of this experiment was to study the effects of replacing a portion of SBM with FSM on nutrient digestibility, rumen microbial protein synthesis and growth performance in sheep. Thirty-six Dorper × Small Thin-Tailed crossbred rams (BW = 40.4 ± 1.73 kg, mean ± SD) were randomly assigned into four groups. The dietary treatments (forage/concentrate, 45 : 55) were isocaloric according to the nutrient requirements of rams. Soybean meal was replaced with FSM at different levels (DM basis): (1) 18% SBM (18SBM), (2) 12% SBM and 6% FSM (6FSM), (3) 6% SBM and 12% FSM (12FSM) and (4) 18% FSM (18FSM). The rams were fed in individual pens for 60 days, with the first 10 days for adaptation to diets, and then the digestibility of nutrients was determined. There was no significant difference in DM intake, but quadratic (P < 0.001) effects on the average daily gain and feed efficiency were detected, with the highest values in the 6FSM and 12FSM groups. For DM and NDF digestibility, quadratic effects were observed with the higher values in the 6FSM and 12FSM groups, but the digestibility of CP linearly decreased with the increase in FSM in the diet (P = 0.043). There was a quadratic (P < 0.001) effect of FSM inclusion rate on the estimated microbial CP yield. However, the values of intestinally absorbable dietary protein decreased linearly (P < 0.001). For the supply of metabolisable protein, both the linear (P = 0.001) and quadratic (P = 0.044) effects were observed with the lowest value in the 18FSM group. Overall, the results indicated that SBM can be effectively replaced by FSM in the diets of fattening sheep and the optimal proportion was 12.0% under the conditions of this experiment.

Replacing alfalfa hay with dry corn gluten feed and Chinese wild rye grass: Effects on rumen fermentation, rumen microbial protein synthesis, and lactation performance in lactating dairy cows.

This experiment was conducted to investigate nutrient digestibility, rumen microbial protein synthesis, and lactation performance when a portion of alfalfa was replaced with combinations of dry corn gluten feed (DCGF) and Chinese wild rye grass in the diet of lactating cows. Six multiparous and 3 primiparous Chinese Holsteins were arranged in a replicated 3 × 3 Latin square experiment for 21-d periods. The animals were fed 1 of 3 treatment diets during each period: (1) 0% DCGF (0DCGF); (2) 6.5% DCGF (7DCGF); and (3) 11% DCGF (11DCGF). Diets were isonitrogenous, and a portion of alfalfa hay was replaced with DCGF and Chinese wild rye grass, with similar concentrate mixtures and corn silage contents. The dry matter intake was greater for 11DCGF (21.9 kg/d) than for 0DCGF (20.7 kg/d) or 7DCGF (21.2 kg/d). The treatment diets did not result in difference in milk production, fat and lactose concentration, or yield. Compared with 0DCGF, the ration containing 11% DCGF improved the milk protein concentration. Dry matter and neutral detergent fiber digestibility was greater for 7DCGF (62.7% and 45.6%) and 11DCGF (63.1% and 47.2%) than for 0DCGF (59.4% and 42.3%), and the nitrogen digestibility was similar for the 3 treatments. The concentration of rumen volatile fatty acids was higher in cows fed the 11DCGF diet than in those fed the 0DCGF diet, with no difference between the 7DCGF and 11DCGF diets. The estimated microbial crude protein yield was greater for the 11DCGF diet (1985.1 g/d) than for the 0DCGF diet (1745.0 g/d), with no difference between the 0DCGF and 7DCGF diets. Thus, it appears that feeding DCGF and Chinese wild rye grass in combination can effectively replace a portion of alfalfa hay in the rations of lactating dairy cows.

[The clinical features and prognosis of nasal Schwannoma].

Objective:To investigate the experience of nasal Schwannoma in order to provide guidance for the diagnosis and treatment of the disease. Method:Clinicopathological data and follow-up results of nine patients, which histopathology proved nasal Schwannoma were collected and analyzed. Result:The patients were referred to our clinic due to the space-occupying symptoms or signs of tumour compression. There were no specific findings in imaging examination. The patients were treated by operation except a multiple Schwannoma patient.The recurrence after operation were rare. The main features of pathological diagnosis was a strong expression of S-100 protein. Conclusion:Nasal Schwannoma usually has no specific clinical manifestations. Imaging examination is valuable to the determination of surgical range and the diagnosis of benign and malignant diseases. The diagnosis depends on histologic examination. Surgery is the only effective treatment. The best surgical procedure selection hinges on the lesion location and the prognosis is excellent.

[Clinical application value of echocardiography combined with genetic testing in fetal cardiac rhabdomyoma].

OBJECTIVE: To investigate the clinical value of echocardiography combined with genetic testing in the fetal cardiac rhabdomyoma. METHODS: Thirty-three fetal cardiac rhabdomyoma cases diagnosed by fetal echocardiogram in Beijing Anzhen Hospital from Jan. 2011 to Oct. 2015 were enrolled in a retrospective analysis. The results of other examination and pregnancy outcomes of them were followed up, the genetic characteristics of cardiac rhabdomyoma were summarized on the basis of pathology and genetics examination results. RESULTS: The pregnancy outcomes: 24 cases were terminated pregnancy, 4 cases were born and 5 cases were lost. The results of ultrasound, pathology and genetic examination were detailed in 8 cases. Pathological examination: the typical characteristics of cardiac rhabdomyoma were found in the 8 cases with cardiac rhabdomyoma. The tumor tissue was composed of irregular and swelling shape of cardiomyocytes, and the cytoplasm was vacuole like, which was characteristic of " spider like cells" through microscopic observation. The geneticdetection results: 7 cases had tuberous sclerosis complex (TSC) gene mutation, TSC gene abnormalities were not detected in 1 case. Among the 7 cases with TSC gene mutations, 6 cases were with TSC2 gene mutation and the other 1 case was with TSC1 gene mutation. The family gene was investigated in the 5 cases, which including 3 cases of TSC gene mutation in mother passed on to the fetus (1 case with family of three generations of genetic) and 2 cases of spontaneous TSC gene mutation in the fetus. CONCLUSIONS: Prenatal echocardiography combined with genetic detection have important clinical significance, which not only can clear if cardiac rhabdomyomas were associated with TSC, but also can clear the TSC gene mutation source. So as to further guide the perinatal management.

Effect of lipoic acid combined with paclitaxel on breast cancer cells.

Breast cancer is the most common gynecologic tumor globally that threatens women's health. Lipoic acid is a type of antioxidant that can alleviate oxidative stress damage. Studies showed that lipoic acid could inhibit the proliferation of tumor cells in cervical cancer and colon cancer. This paper intends to explore the combined effect of lipoic acid and paclitaxel on breast cancer cells. Breast cancer MCF-7 cells were divided into four groups: control group, lipoic acid group, paclitaxel group, and a combination group. MTT was applied to detect the drugs' influence on breast cancer cell proliferation. A colony formation test was used to determine the effects on breast cancer cell clone formation rate. Western blot was performed to detect the effects on nuclear factor (NF)-κB. Lipoic acid alone can inhibit tumor cell proliferation and clone formation with time dependence. Compared with the control, paclitaxel alone can significantly suppress tumor cell proliferation and clone formation (P < 0.05). Lipoic acid and paclitaxel in combination obviously strengthened their individual inhibitory effects on tumor cells (P < 0.05). Compared with the paclitaxel alone group, the combination group exhibited more remarkable inhibitory effect (P < 0.05). Lipoic acid alone or combined with paclitaxel can inhibit NF-κB expression and inhibit breast cancer cell proliferation.

Synergy of aminoglycoside antibiotics by 3-Benzylchroman derivatives from the Chinese drug Caesalpinia sappan against clinical methicillin-resistant Staphylococcus aureus (MRSA).

The in vitro antimicrobial activities of three 3-Benzylchroman derivatives, i.e. Brazilin (1), Brazilein (2) and Sappanone B (3) from Caesalpinia sappan L. (Leguminosae) were assayed, which mainly dealt with synergistic evaluation of aminoglycoside and other type of antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) by the three compounds through the Chequerboard and Time-kill curve methods. The results showed that Compounds 1-3 alone exhibited moderate to weak activity against methicillin-susceptible S. aureus (MSSA) and other standard strains by MICs/MBCs ranged from 32/64 to >1024/>1024 µg/ml, with the order of activity as 1>2>3. Chequerboard method showed significant anti-MRSA synergy of 1/Aminoglycosides (Gentamicin, Amikacin, Etimicin and Streptomycin) combinations with (FICIs)50 at 0.375-0.5. The combined (MICs)50 values (µg/ml) reduced from 32-128/16-64 to 4-8/4-16, respectively. The percent of reduction by MICs ranged from 50% to 87.5%, with a maximum of 93.8% (1/16 of the alone MIC). Combinations of 2 and 3 with Aminoglycosides and the other antibiotics showed less potency of synergy. The dynamic Time-killing experiment further demonstrated that the combinations of 1/aminoglycoside were synergistically bactericidal against MRSA. The anti-MRSA synergy results of the bacteriostatic (Chequerboard method) and bactericidal (time-kill method) efficiencies of 1/Aminoglycoside combinations was in good consistency, which made the resistance reversed by CLSI guidelines. We concluded that the 3-Benzylchroman derivative Brazilin (1) showed in vitro synergy of bactericidal activities against MRSA when combined with Aminoglycosides, which might be beneficial for combinatory therapy of MRSA infection.

Efficient isolation of high-quality RNA from lotus Nelumbo nucifera ssp nucifera tissues.

Nelumbo nucifera is widely used as food, as an ornamental, in medicine, and as packing material; it is also reported to have anti-HIV effects and antioxidant capacity. We sought an improved method for extracting high-quality total RNA from different tissues of N. nucifera. Four methods for RNA extraction were assessed for their ability to recover high-quality RNA applicable for evaluation of polyphenol oxidase (PPO) gene expression profiles. The recovery and quality of the RNA obtained from five different tissues by the best CTAB-LiCl method were evaluated through UV light absorbance. Both A(260)/A(280) and A(260)/A(230) absorbance ratios were more than 2.0; the yield ranged from 59.87 to 163.75 µg/g fresh weight. The brightness of the 28S band was approximately twice that of 18S; the latter was also considered as high-quality RNA. The PPO gene fragment (606 bp) was successfully amplified by RT-PCR, demonstrating the integrity of the isolated RNA. The relative expression levels of the PPO gene based on RT-PCR in five tissues of lotus were: rhizome buds (2.66), young leaves (2.42), fresh cut rhizome (2.02), petals (1.80), and petiole (1.65), using housekeeping gene ß-actin as an internal control. We concluded that the total RNA isolated by this protocol is of sufficient quality for molecular applications.

Molecular Characterization and Tissue-specific Expression of a Novel FKBP38 Gene in the Cashmere Goat (Capra hircus).

As a member of a subclass of immunophilins, it is controversial that FKBP38 acts an upstream regulator of mTOR signaling pathway, which control the process of cell-growth, proliferation and differentiation. In order to explore the relationship between FKBP38 and mTOR in the Cashmere goat (Capra hircus) cells, a full-length cDNA was cloned (GenBank accession number JF714970) and expression pattern was analyzed. The cloned FKBP38 gene is 1,248 bp in length, containing an open reading frame (ORF) from nucleotide 13 to 1,248 which encodes 411 amino acids, and 12 nucleotides in front of the initiation codon. The full cDNA sequence shares 98% identity with cattle, 94% with horse and 90% with human. The putative amino acid sequence shows the higher homology which is 98%, 97% and 94%, correspondingly. The bioinformatics analysis showed that FKBP38 contained a FKBP_C domain, two TPR domains and a TM domain. Psite analysis suggested that the ORF encoding protein contained a leucine-zipper pattern and a Prenyl group binding site (CAAX box). Tissue-specific expression analysis was performed by semi-quantitative RT-PCR and showed that the FKBP38 expression was detected in all the tested tissues and the highest level of mRNA accumulation was detected in testis, suggesting that FKBP38 plays an important role in goat cells.

Antibacterial and synergy of a flavanonol rhamnoside with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

The in vitro antibacterial activity of taxifolin-7-O-α-L-rhamnopyranoside (TR) and its synergy with four conventional antibiotics (ampicillin (AMP), levofloxacin (LEV), ceftazidime (CAZ) and azithromycin (AZM)) against ten clinical isolates of methicillin-resistant staphylococcus aureus (MRSA) were evaluated, respectively. Individual MICs and MBCs were determined by microdilution methods following the CLSI guidelines. Anti-MRSA synergy effects were measured using the chequerboard and time-kill curve tests. MICs/MBCs (µg/ml) ranges were 32-64/64-128 for TR alone against all 10 MRSA isolates. Chequerboard method showed that significant synergies were observed for the TR/CAZ and TR/LEV combinations with FICI ranged 0.187-0.375 and 0.25-0.5, respectively. Some synergy and additivity effects were also observed for TR/AMP and TR/AZM combinations. In the time-kill dynamic confirmation test, synergy results kept by the TR/CAZ combination (2.186 log10 cfu/ml increase in killing), but the TR/LEV combination changed to additivity (1.839 log10 cfu/ml increase in killing). These results demonstrated that TR enhanced the efficacy of CAZ and LEV in vitro, which had potential for combinatory therapy of patients infected with MRSA.

Screening of Chinese medicinal plants for inhibition against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA).

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbs are a valuable source of novel antibacterials in combating pathogenic isolates of methicillin-resistant Staphylococcus aureus (MRSA), a global nosocomial problem. AIM OF THE STUDY: To assess in vitro anti-MRSA activity of extracts from Chinese herbs. The minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were determined in the setting of clinical MRSA isolates. MATERIALS AND METHODS: A collection of 19 plant extracts were obtained and bioassay-guided phytochemical analysis performed. Antibacterial susceptibilities were screened for inhibitory zone and MICs/MBCs determined by serial dilution with a standardized microdilution broth methodology. 9 MRSA isolates and a standard control strain (ATCC 25923) were cultured and exposed to the plant extract and isolated compound. Vancomycin was used as a positive control agent. RESULTS: All the presented 19 plants showed anti-MRSA activity with MIC of 1.25-3.07mg/ml. The most active antimicrobial plants were Dendrobenthamia capitata, Elsholtzia rugulosa, Elsholtzia blanda, Geranium strictipes and Polygonum multiflorum (MIC< or =1.43mg/ml), and betulinic acid isolated from the active ethyl acetate fraction of Dendrobenthamia capitata extract was determined with MIC/MBC values as 62.5/125.0mg/ml. CONCLUSIONS: Dendrobenthamia capitata, Elsholtzia rugulosa, Elsholtzia blanda, Geranium strictipesPolygonum multiflorum and betulinic acid demonstrate promising anti-MRSA potential.

Correlation between CSWS and aphasia in Landau-Kleffner syndrome: a study of three cases.

We report three typical cases of Landau-Kleffner syndrome with varied courses. The very frequent discharges in sleep EEGs, often showing the patterns of CSWS (continuous spike-waves during slow-wave sleep), either typical (spike-wave complex occupying over 85% of slow-wave sleep duration) or atypical (spike-waves occupying less than 85% of slow-wave sleep), were presented in all our cases. The CSWS seems correlated with aphasia in our cases. Since the disappearance of CSWS might be indicative of a lagged improvement in aphasia, we suggest that sufficiently long-term treatment with anticonvulsants and/or corticosteroids is worthwhile, if the EEG is improved significantly by this treatment.

Increased cisplatin sensitivity of human fibroblasts from a subject with inherent glutathione deficiency.

Fibroblasts from an individual with 5-oxoprolinuria are deficient in glutathione (GSH) as compared to cells from a healthy sibling. Glutathione transferase (GST) levels also differ for some isoenzymes: GSH deficient cells have more GST A1-1, but lack GST M1-1. However, the contents of the quantitatively dominating isoenzyme GST P1-1 show no significant difference. While there is equal sensitivity to ultaviolet irradiation (UV), the GSH deficient cells are more sensitive to cisplatin, carboplatin and melphalan. Depletion of GSH with buthionine sulfoximine sensitizes the normal fibroblasts to these drugs. Only slightly more cisplatin-induced DNA cross-links are detected in the GSH deficient cells, and there is no difference in the removal of DNA cross-links. Similar amounts of DNA strand breaks are seen in normal and GSH deficient cells after UV exposure, but there is a reduced rates of resealing of strand breaks in GSH deficient cells. The main conclusion from the studies of these fibroblasts is that GSH plays a significant role in the cellular resistance to cytostatic drugs such as platinum compounds and melphalan.

The expression of glutathione transferase isoenzymes in human malignant lymphoma biopsies.

Glutathione transferase (GST) activity as well as the expression of different classes of GST isoenzymes were studied in 14 lymphoma biopsies. The GST activity measured with 1-chloro-2,4-dinitrobenzene as a substrate, varied almost 9-fold. The expression of GSTs classes Pi, Alpha and Mu was studied by immunoblotting using antibodies against human GSTs. All lymphoma samples displayed high levels of class Pi GST. Class Alpha and Mu GSTs expression varied from not detectable to high. The observations were confirmed by quantitation of the three classes of GST with an ELISA technique. Nine of the patients were treated with bifunctional alkylating agents. A correlation between a clinical complete response to chemotherapy and low expression of GST Alpha was noted (p < 0.02).

Acquired resistance to cisplatin and doxorubicin in a small cell lung cancer cell line is correlated to elevated expression of glutathione-linked detoxification enzymes.

A human small cell lung cancer cell line, U-1906, developed altered functional properties upon continuous in vitro cultivation. Cells obtained at late (U-1906 L) and early (U-1906 E) passages of cultivation differ in drug resistance to the cytostatic therapeutic agents cisplatin and doxorubicin. The U-1906 L cells are 1.6-fold and 1.3-fold more resistant to cisplatin and doxorubicin respectively, than are the U-1906 E cells. In the more resistant U-1906 L cells, the total glutathione (GSH plus GSSG) level is 40% lower, whereas the activities of GSH-linked enzymes such as GSH peroxidase and GSH transferases are significantly higher. Quantitative analysis with isoenzyme-specific ELISAs demonstrated increased concentrations of all three of the measurable GSTs, M1-1, M3-3 and P1-1, in the more resistant cells. The intracellular protein expression patterns of the U-1906 E and the U-1906 L cells are very similar as revealed by two-dimensional denaturing electrophoresis, but show significant alterations in the concentrations of some components. Two 35 kDa proteins of different pI values, the concentrations of which are increased in the U-1906 L cells, were both identified as glyceraldehyde-3-phosphate dehydrogenase, either by N-terminal or by internal amino acid sequence analysis. The present study demonstrates that the increased resistance of the U-1906 L cells may involve multiple detoxification mechanisms and that the contribution of the GSH-linked detoxification can be ascribed to the elevation of cytosolic GST isoenzymes, GSH peroxidase and glutathione reductase, rather than to the intracellular GSH concentrations.