DN4 questionnaire as a useful tool for evaluating the pharmacotherapeutic response to opioid pharmacotherapy in malignant neuropathy.

Objective: Tapentadol is a drug of choice for neuropathic cancer pain. DN4 questionnaire quickly determines neuropathic pain component. The aim of this study is to determine the correlation between neuropathic malignant pain component by applying tapentadol antidolorose pharmacotherapy in combination with palliative radiotherapy of osseous neuropathic metastatic changes in breast cancer patients before and after palliative radiotherapy. Methods: The first patients group comprised 30 patients with primary breast cancer and proved painful bone secondary deposits with neuropathy for which tapentadol was prescribed, and they underwent palliative radiotherapy. The second group comprised 30 patients with primary breast cancer and proved painful bone metastases with neuropathy treated only with palliative antidolorose radiotherapy. Key findings : After two-months-follow up, tapentadol group patients had lower DN4 score values (Z=2,021; p=0.043). Significantly lower number of tapentadol group patients was without neuropathic pain after a three-month-follow up (χ ²=5,711; p=0.017). Significantly greater number of tapentadol group patients had best ECOG score 0 ( χ² =7,486; p=0.023). There was statistically significant positive correlation between tapentadol dose and DN4 score in patients after a month (ρ=0,471; p=0.009) and three months after the radiotherapy completion (ρ=0,610; p<0.001). Tapentadol is an opioid analgesic efficient for neuropathy relief in these patients and DN4 questionnaire is an efficient pharmacotherapy tool.

The role of tapentadol in cancer pain pharmacotherapy in patients with metastatic malignant disease.

OBJECTIVE: The aim of this study was to establish the effects of prolonged formulation of tapentadol in combination with palliative radiotherapy on bone metastatic changes in oncology patients with primary breast cancer and proven bone metastases. PATIENTS AND METHODS: The research was conducted as a prospective study at the Clinic for Oncology, University Clinical Center Nis, Nis, Serbia, during a three-month interval of monitoring the patients. The first group comprised 30 patients with mentioned malignancy for which tapentadol was prescribed, and they underwent palliative radiotherapy for bone metastatic changes. The second group comprised 30 patients with the same disease treated only with pain relief radiotherapy to metastatic changes. All the patients were interviewed using the Pain Detect questionnaire. RESULTS: Significantly more patients from the first group had severe pain in comparison to patients from the control group (χ2=16.596; p<0.001) at the second measurement and also at the third measurement (χ2=15.357; p<0.001). At the third measurement, pain with a neuropathic component was significantly more present in patients from the control group (χ2=8.541; p=0.014). There was a significant pain reduction in both groups - Tapentadol group (χ2=59.513; p<0.001) and control group (χ2=60.000; p<0.001) - and also a significant reduction of neuropathic pain component: Tapentadol group (χ2=56.267; p<0.001) and control group (χ2=60,000; p<0.001). There was a statistically significant positive correlation between tapentadol dose and pain intensity according to the numerical pain scale at all three measurements. CONCLUSIONS: Tapentadol prolonged-release formulation is an effective pharmacotherapy solution, along with palliative radiotherapy, for pain relief in patients with skeletal metastatic breast cancer. Palliative radiotherapy in these patients does not provide adequate neuropathic pain component relief.

Protective effects of whey on rat liver damage induced by chronic alcohol intake.

In 2012, alcohol liver disease resulted in 3.3 million-5.9% of global deaths. This study introduced whey protection capacity against chronic alcohol-induced liver injury. Rats were orally administered to 12% ethanol solution in water (ad libitum, average 8.14 g of ethanol/kg body weight (b.w.)/day) alone or combined with whey ( per os, 2 g/kg b.w./day). After 6-week treatment, chronic ethanol consumption induced significant histopathological liver changes: congestion, central vein dilation, hepatic portal vein branch dilation, Kupffer cells hyperplasia, fatty liver changes, and hepatocytes focal necrosis. Ethanol significantly increased liver catalase activity and glutathione reductase protein expression without significant effects on antioxidative enzymes: glutathione peroxidase (GPx), copper-zinc-containing superoxide dismutase (CuZnSOD) and manganese-containing superoxide dismutase (MnSOD). Co-treatment with whey significantly attenuated pathohistological changes induced by ethanol ingestion and increased GSH-Px and nuclear factor kappa B (NF-κB) protein expression. Our results showed positive effects of whey on liver chronically exposed to ethanol, which seem to be associated with NF-κB-GPx signaling.

Underlying theory of a model for the Renner-Teller effect in tetra-atomic molecules: X(2)Πu electronic state of C2H2(+).

In the present study, we prove the plausibility of a simple model for the Renner-Teller effect in tetra-atomic molecules with linear equilibrium geometry by ab initio calculations of the electronic energy surfaces and non-adiabatic matrix elements for the X(2)Πu state of C2H2 (+). This phenomenon is considered as a combination of the usual Renner-Teller effect, appearing in triatomic species, and a kind of the Jahn-Teller effect, similar to the original one arising in highly symmetric molecules. Only four parameters (plus the spin-orbit constant, if the spin effects are taken into account), which can be extracted from ab initio calculations carried out at five appropriate (planar) molecular geometries, are sufficient for building up the Hamiltonian matrix whose diagonalization results in the complete low-energy (bending) vibronic spectrum. The main result of the present study is the proof that the diabatization scheme, hidden beneath the apparent simplicity of the model, can safely be carried out, at small-amplitude bending vibrations, without cumbersome computation of non-adiabatic matrix elements at large number of molecular geometries.

Bias spectroscopy and simultaneous single-electron transistor charge state detection of Si:P double dots.

We report a detailed study of low-temperature (mK) transport properties of a silicon double-dot system fabricated by phosphorous ion implantation. The device under study consists of two phosphorous nanoscale islands doped to above the metal-insulator transition, separated from each other and the source and drain reservoirs by nominally undoped (intrinsic) silicon tunnel barriers. Metallic control gates, together with an Al-AlO(x) single-electron transistor (SET), were positioned on the substrate surface, capacitively coupled to the buried dots. The individual double-dot charge states were probed using source-drain bias spectroscopy combined with non-invasive SET charge sensing. The system was measured in linear (source-drain DC bias V(SD) = 0) and non-linear (V(SD) ≠ 0) regimes, allowing calculations of the relevant capacitances. Simultaneous detection using both SET sensing and source-drain current measurements was demonstrated, providing a valuable combination for the analysis of the system. Evolution of the triple points with applied bias was observed using both charge and current sensing. Coulomb diamonds, showing the interplay between the Coulomb charging effects of the two dots, were measured using simultaneous detection and compared with numerical simulations.

Diurnal urinary excretion of cortisol and aldosterone in kidney graft recipients.

In 13 supine kidney graft recipients in the late post-transplant period the circadian rhythms of urinary cortisol and aldosterone excretion were studied. An inversion of the circadian rhythm of urinary cortisol excretion was found, with acrophase occuring in the night time. Plasma cortisol level, measured in 6 h intervals, attained the maximal mean value at 24 h. Urinary aldosterone excretion in most of the patients demonstrated also an inversed circadian rhythm with acrophase occuring from 21 to 03 h. In 6 patients the 24 h urinary aldosterone excretion was above the upper limit for healthy persons. The peak plasma aldosterone level was found at 24 h; it greatly exceeded the upper limit of aldosterone level in healthy supine persons. In 5 out of 13 patients the plasma renin activity (PRA) was above the upper limit of normal for supine subjects. The maximal mean PRA level was found at 24 h. The study in kidney graft recipients has established an inversed circadian rhythm of urinary cortisol and aldosterone excretion, probably related to the immunosuppressive treatment and reduced kidney function.

Receptor-mediated induction of human glomerular epithelial cell alkaline phosphodiesterase I by glucocorticoids.

Alkaline phosphodiesterase I was demonstrated in human glomerular mesangial cells (HGEC) as an ectoenzyme. Treatment of HGEC by dexamethasone increased surface phosphodiesterase I activity in a dose- and time-dependent manner. Maximal increase of phosphodiesterase I activity, about twice, occurred after treatment with 5 microM dexamethasone for 6 days. Cycloheximide prevented and RU 38486, a glucocorticoid receptor antagonist, suppressed the dexamethasone induced increase in phosphodiesterase I activity. This study shows that HGEC have a surface phosphodiesterase I controlled by glucocorticoids through a receptor-mediated mechanism.

Cytokine levels in patients with urinary tract cancer.

It is known that cytokine exert cytotoxic effect on certain tumor cell lines, as well as that cytokines production might be influenced by tumor cells. Therefore, serum and urine levels of TNF and IL-1 were determined by RIA in 20 patients with upper urinary tract cancer, 26 with urinary bladder cancer, and compared with those of 52 healthy blood bank donors. Serum levels of TNF in cancer patients were found moderately increased, and those of IL-1 unchanged. Conversely, urinary excretion of TNF was shown decreased in both upper urinary tract and urinary bladder cancer patients, while IL-1 excretion was not significantly changed. Tumor grade was not found to influence serum and urine levels of the cytokines studied. Unstimulated and PHA- and Con A-stimulated production of TNF by peripheral blood mononuclear cells was within the normal range, suggesting that other sources such as tumor cells have to be considered for the increase in the serum level. Basal production of IL-1 was lowered in patients with upper urothelial cancer. Further investigation are required to ascertain and reveal the possible mechanism of the decreased urinary excretion associated with increased serum levels of TNF in urinary tract cancer.

Myoglobin elimination in end stage kidney disease patients on renal replacement treatment.

Increased serum myoglobin levels were previously found in patients with chronic renal failure. In this report we have studied the effects of dialysis on myoglobin elimination in patients on CAPD, IPD, cuprophan and polyacrylonitrile (PAN) membrane hemodialysis. Peritoneal dialysis removed a significant amount of myoglobin, CAPD 480 +/- 65 micrograms/day, IPD 270 +/- 25 micrograms/12 h treatment, while with cuprophan dialysis none, and with PAN dialysis only an insignificant amount of myoglobin. The serum myoglobin levels were 250 +/- 18 and 264 +/- 14 micrograms/l on cuprophan and a 3 month dialysis on PAN membrane, respectively. Markedly increased serum levels were also found in CAPD and IPD patients on peritoneal dialysis, 227 +/- 25 and 286 +/- 32 micrograms/l respectively. This study has shown that there is an increased serum myoglobin concentration in end-stage kidney disease patients on dialysis. Although peritoneal membrane is permeable to myoglobin, a relatively small amount is removed, and the serum level in CAPD and IPD patients was not significantly different from the serum myoglobin concentration in hemodialysis patients. Furthermore myoglobin could not be removed by hemodialysis membrane and an analysis of its important extrarenal catabolism level points were analyzed.

Beta 2-microglobulin elimination in end-stage renal disease patients on renal replacement therapy.

beta 2-microglobulin (beta 2M) is a small molecular mass protein associated with dialysis amyloidosis. We have studied beta 2M elimination in end-stage renal disease (ESRD) patients treated by peritoneal dialysis. In 12 patients on continuous ambulatory peritoneal dialysis (CAPD) and 7 patients on intermittent peritoneal dialysis (IPD) 30.4 +/- 4.2 mg/day and 21.3 +/- 1.8 mg/12 hour of beta 2M, respectively, were removed by dialysis fluid. Approximately the same amount of beta 2M was removed by each of four 2-L exchanges in CAPD; however, the most efficient removal of beta 2M was in the first IPD exchange. Serum beta 2M levels in these patients were 25.7 +/- 4.4 and 31.4 +/- 5.2 mg/L, respectively. In 24 patients on hemodialysis using cuprophan membrane the serum level of beta 2M was 55.1 +/- 4.1 mg/L. After a 3-month dialysis on polyacrylonitrile (PAN) membrane, the serum beta 2M level decreased to 45.0 +/- 2.3 mg/L. A substantial amount of beta 2M was removed by urine, 14.6 +/- 2.3 mg/L, and saliva, 2.3 +/- 0.4 mg/L. This study has shown markedly increased beta 2M levels in patients on conventional hemodialysis treatment, predisposing to beta 2M-related amyloidosis. A significant amount of beta 2M was removed during both CAPD and IPD treatment.

[Diurnal changes in the levels of immunoreactive parathyroid hormone and calcitonin in patients with chronic renal insufficiency]. / Dnevne promene koncentracije imunoreaktivnog paratireoidnog hormona i kalcitonina bolesnika s hronicnom bubreznom insuficijencijom.

The circadian rhythms of the serum immunoreactive parathyroid hormone (iPTH) and calcitonin concentration were examined in 6 patients with chronic renal failure (CRF) not treated by haemodialysis. In 3 patients on haemodialysis the influence of haemodialysis with cuprophan and polyacrylonitrile membranes (in a.m. and p.m. periods of day) on serum concentration of these was investigated. The results demonstrate that in patients with CRF in predialysis period the circadian rhythm of serum iPTH concentration is at least partially preserved. However, the effect of dialysis on serum C-terminal iPTH concentration showed a sharp progressive fall of the concentration during haemodialysis on polyacrylonitrile membranes. The study of the circadian rhythm of serum calcitonin concentration in CRF patients with the six hours intervals between blood sampling could not reveal changes which favour the opinion of the existence of circadian rhythmicity. In patients on haemodialysis during haemodialysis with cuprophan membranes a rise of serum calcitonin concentration was observed.