According to World Health Organization (WHO), trypanosomiasis and leishmaniasis are the most challenging among the neglected tropical diseases. Comparative studies between Leishmania spp and ...Trypanosoma cruzi have been conducted aiming to find a broad spectrum antiprotozoal agent acting against both parasites. Among the potential molecular target, Trypanothione reductase (TR) is considered an ideal enzyme since it is involved in the unique thiol-based metabolism observed in the Trypanosomatidae family and is a validated target for the search of antitrypanosomatidae drugs. In this review we intend to describe the currently available therapy to treat trypanosomatidae diseases and to highlight important aspects of trypanothione reductase as a target for the search of new and selective inhibitors, such as tricyclic, diphenylsulfide, bicyclic and heterocyclic, polyamine, natural product, N-oxide and nitroheterocyclic, aryl β-aminocarbonyl and α,β-unsaturated carbonyl derivatives.
New bioemulsifier-producing yeasts were isolated from the biological wastewater treatment plant of a dairy industry
. Of the 31 bioemulsifier-producing strains, 12 showed emulsifying activity after 2
...months of incubation, with
E
24 values ranging from 7% to 78%. However, only
Trichosporon loubieri CLV20,
Geotrichum sp. CLOA40, and
T. montevideense CLOA70 exhibited high emulsion-stabilizing capacity, with
E
24 values of 78%, 67%, and 66%, respectively. These isolates were shown to induce a strong emulsion stabilizing activity rather than the reduction of the interfacial tension. These strains exhibited similar growth rates in the exponential growth phase, with a clear acceleration after 24
h and stabilization of the activity after 144
h. Emulsification and stability properties of the bioemulsifiers were compared to those of commercial surfactants after the addition of NaCl and exposure to temperature of 100
°C. The compounds produced by the isolates appeared to be lipid–polysaccharide complexes. Gas chromatograph analysis of the lipidic fraction of the bioemulsifiers from CLV20, CLOA40, and CLOA70 shows the prevalence of (9
Z,12
Z)-octadeca-9,12-dienoic acid, in concentrations of 42.8%, 25.9%, and 49.8%, respectively. The carbohydrate composition, as determined by GC–MS of their alditol acetate derivatives, showed a predominance of mannose, galactose, xylose and arabinose.
Hypercalcemia and hyperphosphatemia often complicate secondary hyperparathyroidism therapy in patients who are receiving dialysis. Unlike vitamin D and calcium, calcimimetic agents target the ...calcium-sensing receptor. This study reports the safety and effectiveness of the calcimimetic agent cinacalcet in patients receiving dialysis who had uncontrolled hyperparathyroidism. The mean parathyroid hormone values decreased 43 percent with cinacalcet therapy but increased 9 percent with placebo, and the calcium–phosphorus product declined with cinacalcet but not placebo.
The safety and effectiveness of a calcimimetic agent in patients receiving dialysis.
Secondary hyperparathyroidism is common in patients with chronic kidney disease, affecting most of those who are receiving hemodialysis.
1
,
2
The disorder is characterized by persistently elevated levels of parathyroid hormone and complicated by important disturbances in mineral metabolism.
3
Bone disease is the most widely recognized consequence of secondary hyperparathyroidism.
4
Several reports indicate, however, that alterations in calcium and phosphorus metabolism, as a result of either secondary hyperparathyroidism or the therapeutic measures used to manage it, contribute to soft-tissue and vascular calcification, cardiovascular disease, and the risk of death.
5
–
10
Episodes of hypercalcemia and hyperphosphatemia are often aggravated by the use . . .
Aim: To evaluate compliance in children with acute lymphoblastic leukaemia (ALL). Methods: Compliance was assessed through specific interviews, annotations from medical charts, and erythrocytic ...determination of 6-mercaptopurine metabolites. Results: A total of 39 patients who had concluded maintenance phase of chemotherapy were included in the study. Mothers were responsible for delivering 6-MP in 87% of cases. Thirty five interviewees said that medical prescription was well understood and that the main reason for non-compliance was forgetfulness. Non-compliance was detected through interviews (33.3% of the cases), reports from medical charts (30.7%), and drug determination (16.6%); 53.8% of children were found to be non-compliant. Non-compliance was significantly associated with chronic undernourishment. Although not statistically significant, there was a trend for the group of non-compliant children to be associated with low per capita family income. No significant associations of non-compliance with age at diagnosis, gender, parents’ schooling level, number of family members, power consumption, and medians of absolute leucocyte or neutrophil blood counts were detected. A short follow up period precluded valid analysis on outcome. In the non-compliant group (n = 21), seven children relapsed, contrasting with three relapses in the compliant group (n = 18). Conclusions: Results suggest that non-compliance is one of the mechanisms which underlies the adverse influence of socioeconomic factors on the outcome of children with ALL. Additional studies are necessary to confirm this hypothesis. Comprehensive approaches to the problem of non-compliance are urgently needed.
Palladium(II) complexes of 2-benzoylpyridine thiosemicarbazone (H2Bz4DH) and its N(4)-methyl (H2Bz4M) and N(4)-phenyl (H2Bz4Ph) derivatives were obtained and fully characterized. Pd(2Bz4DH)Cl (
1) ...crystallizes in the monoclinic space group
P2
1/
c with
a
=
11.671(1),
b
=
10.405(1),
c
=
13.124(1),
β
=
115.60(1)° and
Z
=
4; Pd(2Bz4M)Cl (
2) in the monoclinic space group
P2
1/
c with
a
=
9.695(1),
b
=
15.044(1),
c
=
10.718(1) Å,
β
=
105.38(1)° and
Z
=
4 and Pd(2Bz4Ph)Cl (
3) in the triclinic space group
P
1
¯
with
a
=
9.389(1),
b
=
13.629(1),
c
=
15.218(1) Å,
α
=
70.25(1),
β
=
73.46(1),
γ
=
83.57(1)° and two independent molecules per asymmetric unit (
Z
=
4). All complexes show a quite similar planar fourfold environment around palladium(II). A negatively charged organic molecule acts as a tridentate ligand and binds to the metal through the pyridine nitrogen, the imine nitrogen and the sulfur atom. A chloride ion occupies the fourth coordination site. The planar complexes stack nearly parallel to one another in the lattice conforming a layered crystal structure. The cytotoxic activity of the thiosemicarbazones and their metal complexes was tested against the MCF-7, TK-10 and UACC-62 human tumor cell lines. The ligands exhibit lower values of GI
50 and LC
50 than the complexes, H2Bz4Ph being the most active with GI
50
<
0.003 μM; LC
50
=
13.4 μM; GI
50
=
9.3 μM, LC
50
=
12.9 μM; GI
50
<
0.003, LC
50
=
13.8 μM in the MCF-7, TK-10 and UACC-62 cell lines, respectively. Among the complexes, Pd(2Bz4Ph)Cl (
3) exhibited the lowest values of GI
50 in the three studied cell lines.
In this study, we screened sixty medicinal plant species from the
Brazilian savanna ("cerrado") that could contain useful compounds for
the control of tropical diseases. The plant selection was based ...on
existing ethnobotanic information and interviews with local healers.
Plant extracts were screened for: (a) molluscicidal activity against
Biomphalaria glabrata , (b) toxicity to brine shrimp ( Artemia salina
L.), (c) antifungal activity in the bioautographic assay with
Cladosporium sphaerospermum and (d) antibacterial activity in the agar
diffusion assay against Staphylococcus aureus , Escherichia coli ,
Bacillus cereus and Pseudomonas aeruginosa. Forty-two species afforded
extracts that showed some degree of activity in one or more of these
bioassays.
Piperaceae is a family of tropical plants known to have antifungal, antibacterial, tumour-inhibitory, antiviral, antioxidant, molluscicidal and leishmanicidal activities. In this work, extracts and ...fractions from aerial parts of Piper abutiloides (Piperaceae), a traditional medicinal plant, were evaluated against the fungal species Candida albicans, C. parapsilosis, C. krusei, C. glabrata, C. tropicalis, Cryptococcus neoformans and Sporothrix schenckii. The results have shown that the antifungal activity of this plant can be concentrated in the hexanic fraction after partitioning its hydroalcoholic extract between hexane and 90% aqueous methanol. The chromatographic fractionation of the bioactive part was monitored with a bioautographic assay using C. glabrata, and allowed the isolation of three antifungal compounds: pseudodillapiol, eupomatenoid-6 and conocarpan. These compounds presented different potencies against the fungi tested, with the strongest effect being observed for eupomatenoid-6 against C. glabrata, which presented a minimal inhibitory concentration value of 0.3 μg spot⁻¹. Conocarpan showed antifungal activity without apparent cytotoxic effect on normal human lymphocytes, as assessed by the proliferation assay with human peripheral blood mononuclear cells stimulated with phytohaemaglutinin. This work reveals for the first time the occurrence of these compounds in P. abutiloides and justifies further studies to clarify their mechanisms of action.
Hypnophilin and panepoxydone, terpenoids isolated from Lentinus strigosus, have significant inhibitory activity on Trypanosoma cruzi trypanothione reductase (TR). Although they have similar TR ...inhibitory activity at 10 μg/mL (40.3 μM and 47.6 μM for hypnophilin and panepoxydone, respectively; ~100%), hypnophilin has a slightly greater inhibitory activity (~71%) on T. cruzi amastigote (AMA) growth in vitro as well as on in vitro phytohemagglutinin (PHA)-induced peripheral blood mononuclear (PBMC) proliferation (~70%) compared to panepoxydone (69% AMA inhibition and 91% PBMC inhibition). Hypnophilin and panepoxydone at 1.25 μg/mL had 67% inhibitory activity onLeishmania (Leishmania) amazonensis amastigote-like (AMA-like) growth in vitro. The panepoxydone activity was accompanied by a significant inhibitory effect on PHA-induced PBMC proliferation, suggesting a cytotoxic action. Moreover, incubation of human PBMC with panepoxydone reduced the percentage of CD16(+) and CD14(+) cells and down-regulated CD19(+), CD4(+) and CD8(+) cells, while hypnophilin did not alter any of the phenotypes analyzed. These data indicate that hypnophilin may be considered to be a prototype for the design of drugs for the chemotherapy of diseases caused by Trypanosomatidae.
Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's ...disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults.
The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid β (Aβ) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls.
The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aβ, tau, or p-tau levels, or tau/Aβ or p-tau/Aβ ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 95% CI, -0.06 to 0.43; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (β, -0.31 95% CI, -0.45 to -0.17; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up.
During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aβ) changes or greater cognitive decline.
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