In vitro antiprotozoan activity and mechanisms of action of selected Ghanaian medicinal plants against Trypanosoma,Leishmania, and Plasmodium parasites

Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti‐Trypanosoma, anti‐Leishmania, and anti‐Plasmodium activities in vitro and investigated their mechanisms of action. Twenty‐three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC₅₀ values less than 20 μg/ml. Eleven extracts showed high anti‐Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC₅₀ (selectivity index [SI]) values were 5.51 μg/ml (35.00) and 5.96 μg/ml (13.09), respectively. Nine extracts had high anti‐Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC₅₀ (SI) values were 10.8 μg/ml (1.50) and 10.1 μg/ml (0.37), respectively. Six extracts had high anti‐Plasmodium activity with the leaf and stem‐bark extracts of Terminalia ivorensis recording the highest activity. Their IC₅₀ (SI) values were 7.26 μg/ml (129.36) and 17.45 μg/ml (17.17), respectively. Only M. lucida at 25 μg/ml induced significant apoptosis‐like cell death in Trypanosoma parasites. Anti‐Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.     

Moderate renal dysfunction may not require a cisplatin dose reduction: a retrospective study of cancer patients with renal impairment

Objective

The aim of this study was to assess the tolerability of cisplatin (CDDP) in patients with moderate renal dysfunction.

Methods

To investigate the relationship between CDDP dose and nephrotoxicity, a retrospective chart review was conducted of patients with a creatinine clearance (Ccr) of 30–60 mL/min. Subjects were classified into three groups according to the CDDP dose, as determined by the physician, and the nephrotoxicity among these groups was compared. Additionally, we investigated the correlation coefficients between maximum serum creatinine (Scr) level or minimum estimated glomerular filtration rate (eGFR) and baseline Ccr.

Results

Fifty-six patients were included in this study. Among these patients, 13 patients received 30–40 mg/m² CDDP (group I), 18 patients received 40–70 mg/m² (group II), and 25 patients received 70–80 mg/m² (group III). No significant difference in nephrotoxicity was observed (median Scr 1.53, 1.61, and 1.53 mg/dL, respectively), and no correlation was observed between baseline Ccr and maximum Scr (r = 0.004, p = 0.979) or minimum eGFR (r = 0.21, p = 0.119). Only two patients (3.5 %) experienced grade 3 or 4 Scr elevation—one patient with a Ccr of 52.6 mL/min received 60 mg/m² CDDP, and the other patient with a Ccr of 52.1 mL/min received 70 mg/m² of CDDP. Hemodialysis was not observed.

Conclusion

CDDP was tolerated at doses of 35–80 mg/m² among patients with moderate renal impairment. Empiric dose reduction might create a risk of under-treatment.     

Bioactive Triterpenes from the Root of Salvia miltiorrhiza Bunge

Danshen (Salvia miltiorrhiza) is a well‐known medicinal herb in the oriental medicine. The current study on bioactive triterpenoid in the root of S. miltiorrhiza led to the isolation of a new highly hydroxylated ursane‐type triterpene, urs‐12‐ene‐2α,3β,7β,16α‐tetraol (1) and five known ones including 2β‐hydroxypomolic acid (2), maslinic acid (3), asiatic acid (4), ursolic acid (5), and oleanolic acid (6). Their structures were elucidated on the basis of extensive spectroscopic analyses and comparison with literature data. The antiproliferative testing against HL‐60 cells revealed that the new compound 1 and ursolic acid (5) showed weak and moderate activities with IC₅₀ values of 42.2 and 11.7 μM. In addition, compounds 1–3 showed inhibitory effect on ghrelin activity. Copyright © 2017 John Wiley & Sons, Ltd.     

Primary diffuse leptomeningeal gliosarcomatosis

We report a 48-year-old woman with primary diffuse leptomeningeal gliomatosis (PDLG) histologically diagnosed as gliosarcoma. She was admitted complaining of headache, numbness of the right arm, double vision, and visual field defects. Computerized tomography (CT) scans showed ventricular dilatation consistent with communicating hydrocephalus. Magnetic resonance imaging (MRI) revealed diffuse meningeal thickening and gadolinium enhancement without a definite intraparenchymal lesion. Whole-spine MRI demonstrated across-the-board dural thickening and gadolinium enhancement. Cytological examination showed atypical anaplastic cells. As no diagnosis could be made she underwent biopsy of the leptomeninges. Histological examination of the specimen returned a diagnosis of gliosarcoma. Despite chemotherapy and radiotherapy she died 11 months after admission. Autopsy findings included gliosarcoma in the leptomeninges and spinal cord without an underlying parenchymal tumor. To our knowledge, this is the first report of primary diffuse leptomeningeal gliosarcomatosis.     

Predictability of Conventional Tests for the Assessment of Bladder Outlet Obstruction in Benign Prostatic Hyperplasia

Background The degree of bladder outlet obstruction (BOO) in benign prostatic hyperplasia (BPH) is most accurately quantified by pressure flow studies (PFS), although these studies are more invasive and complicated than conventional tests. We examined how precisely conventional tests predicted the PFS-assessed degree of BOO.
Methods The study population consisted of 232 BPH patients who had undergone routine conventional tests and PFS. Correlation of the conventional test results with the degree of BOO assessed by PFS was examined by Spearman's correlation coefficients. Regression and subgroup analyses were performed to predict the degree of BOO using the conventional test results as the explanatory variables.
Results The degree of BOO correlated with prostate volume, the degree of endoscopic obstruction, and to a lesser extent, with the maximum flow rate ( Q _max) and age. The predictability of conventional tests alone, or in combination, for BOO, was approximately 60% to 70%, which is not acceptable for investigational use. However, almost all patients with a prostate volume larger than 30 mL, or with severe obstruction on urethroscopic findings, had an obstructed bladder outlet.
Conclusion PFS is mandatory when the precise evaluation of the degree of BOO is required, and patients are highly likely to have an outlet obstruction when they have a prostate larger than 30 mL, or severely obstructed posterior urethra on endoscopy.     

Remote effects in the ipsilateral thalamus and/or contralateral cerebellar hemisphere using FDG PET in patients with brain tumors

Purpose

To evaluate reduced metabolism in the ipsilateral thalamus (TH) and/or contralateral cerebellum (CE) according to tumor localization and cortical metabolism around the tumor in patients with brain tumors based on FDG uptake.

Methods

This study investigated 48 consecutive patients with solitary cerebral hemisphere parenchymal brain tumors who underwent PET/CT and MRI. Patients were divided into 4 groups (A: reduced uptake in ipsilateral TH and contralateral CE, B: reduced uptake in ipsilateral TH only, C: reduced uptake in contralateral CE only, and D: no reduced uptake in ipsilateral TH or contralateral CE). FDG uptake and MRI findings were compared among these groups.

Results

Of 48 patients, group A included 24 (50%), group B included 10 (21%), group C included 0, and group D included 14 (29%). No significant tendencies were observed between the groups regarding tumor localization. However, reduced cortical metabolism around the tumor was observed in 22 patients in group A, 7 patients in group B, and 1 patient in group D. All patients in group B showed reduced metabolism from around the tumor up to the ipsilateral TH.

Conclusion

Reduced FDG uptake in ipsilateral TH and contralateral CE usually occur simultaneously in patients with solitary brain tumors.

     

Juxtapapillary Duodenal Diverticulum Impacted with Enterolith

Journal of Gastrointestinal Surgery - A 64-year-old man underwent abdominal computed tomography (CT) as periodic follow-up following a distal gastrectomy with lymphadenectomy for gastric cancer and...