CK2 (official acronym for casein kinase 2 or II) is a potent suppressor of apoptosis in response to diverse apoptotic stimuli —thus its molecular downregulation or activity inhibition results in potent induction of cell death. CK2 downregulation is known to impact mitochondrial apoptotic circuitry but the underlying mechanism(s) remain unclear. Utilizing prostate cancer cell lines subjected to CK2-specific inhibitors which cause loss of cell viability, we have found that CK2 inhibition in cells causes rapid early decrease in mitochondrial membrane potential (Δψm). Cells treated with the CK2 inhibitors TBB (4,5,6,7-tetrabromobenzotriazole) or TBCA (tetrabromocinnamic acid) demonstrate changes in Δψm which become apparent within 2 h, i.e., significantly prior to evidence of activation of other mitochondrial apoptotic signals whose temporal expression ensues subsequent to loss of Δψm. Further, we have demonstrated the presence of CK2 in purified mitochondria and it appears that the effect on Δψm evoked by inhibition of CK2 may involve mitochondrial localized CK2. Results also suggest that alterations in Ca2+ signaling may be involved in the CK2 mediated regulation of Δψm and mitochondrial permeability. Thus, we propose that a key mechanism of CK2 impact on mitochondrial apoptotic circuitry and cell death involves early loss of Δψm which may be a primary trigger for apoptotic signaling and cell death resulting from CK2 inhibition.

BackgroundScreening for neonatal hyperbilirubinaemia in the postnatal ward has traditionally been performed using serum bilirubin sampling, but this has significant drawbacks such as risk of infection and slower reporting time.ObjectiveWe aimed to assess the impact of introducing transcutaneous bilirubin (TcBR) testing using TcBR nomogram on the number of serum bilirubin samples sent.MethodsA before-and-after study was performed following the introduction of a protocol integrating the use of the Dragger JM-105 transcutaneous bilirubinometer in the postnatal ward. Only babies born at ≥37 weeks of gestation, weighing ≥2500 g who presented with jaundice after the first 24 hours and within the first 7 days of life were included in the study. The number of total serum bilirubin samples (TSBRs) sent were compared for the 6-month periods before and after (a total of 12 months) implementation of the new protocol.ResultsIn the pre-implementation phase, a total of 882 (49%) out of 1815 babies had at least one serum bilirubin sample taken as opposed to a total of 236 (17%) out of 1394 babies in the post-implementation phase. The odds of performing TSBRs at least one time among babies in post-implementation phase were 79% lower than in pre-implementation phase (OR 0.21, 95% CI 0.18 to 0.25). We also estimated a significant cost saving of approximately US$1800 over a period of 6 monthsConclusionTcBR testing used in conjunction with our proposed nomogram significantly reduces the need for serum bilirubin sampling.

IntroductionNeonatal jaundice is a common cause of concern in immediate newborn period for parents as well as for the caregivers. Babies with visible jaundice are identified by the healthcare provider, and blood samples are sent for confirmation. Clinical expertise varies from person to person and may lead to sending excessive blood sampling. Obtaining blood bilirubin samples is a painful procedure; it predisposes the baby to infections and requires skilled health personnel. Moreover, laboratory tests are costly and time consuming, leading to unnecessary delays in commencing phototherapy and discharge from hospital. Transcutaneous bilirubinometer has been in use for a long time as screening tool in postnatal wards. With passage of time, its accuracy and validity have improved tremendously.MethodologyWe aim to implement a quality improvement initiative to reduce the number of blood bilirubin samples using transcutaneous bilirubin (TcBR) nomogram in full-term, low-risk babies who are born at our hospital and are admitted in postnatal ward after birth. Using preanalysis and postanalysis study design, this study will be performed in two phases of 6 months each. Data regarding total number of admissions in postnatal wards, demographics, serum bilirubin(TSBR) samplings and need for phototherapy will be recorded in both phases. TcBR will be done and recorded in postimplementation phase.Analysis and resultsComparisons between the two groups will be made. Primary outcome will be reduction in blood bilirubin samples for TSBR after the implementation of TcBr protocol. The proportion of infants having TSBR performed in both periods will be compared. Crude sampling cost of TSBR will be obtained from laboratory, and cost comparison between two phases will be done to look for difference.

Protein kinase CK2 plays a critical role in cell growth, proliferation, and suppression of cell death. CK2 is overexpressed, especially in the nuclear compartment, in the majority of cancers, including prostate cancer (PCa). CK2-mediated activation of transcription factor nuclear factor kappa B (NF-κB) p65 is a key step in cellular proliferation, resulting in translocation of NF-κB p65 from the cytoplasm to the nucleus. As CK2 expression and activity are also elevated in benign prostatic hyperplasia (BPH), we sought to increase the knowledge of CK2 function in benign and malignant prostate by examination of the relationships between nuclear CK2 and nuclear NF-κB p65 protein expression. The expression level and localization of CK2α and NF-κB p65 proteins in PCa and BPH tissue specimens was determined. Nuclear CK2α and NF-κB p65 protein levels are significantly higher in PCa compared with BPH, and these proteins are positively correlated with each other in both diseases. Nuclear NF-κB p65 levels correlated with Ki-67 or with cytoplasmic NF-κB p65 expression in BPH, but not in PCa. The findings provide information that combined analysis of CK2α and NF-κB p65 expression in prostate specimens relates to the disease status. Increased nuclear NF-κB p65 expression levels in PCa specifically related to nuclear CK2α levels, indicating a possible CK2-dependent relationship in malignancy. In contrast, nuclear NF-κB p65 protein levels related to both Ki-67 and cytoplasmic NF-κB p65 levels exclusively in BPH, suggesting a potential separate impact for NF-κB p65 function in proliferation for benign disease as opposed to malignant disease.

RF amide peptide family with distinctive terminal -Arg-Phe-NH(2) signature is evolutionarily conserved from invertebrates to mammals. These neuropeptides have been shown to affect diverse functions in invertebrates and vertebrates including influencing pituitary hormone secretion. More recently, two members of this family 26-amino acid and 43-amino acid RF amide peptide (26RFa and 43RFa, respectively) originally isolated from frog have been cloned in rats and humans. Actions of these peptides on hormone secretion have not been studied in primates. In the present study, effect of iv administration of three different doses of human 26RFa and 43RFa on GH secretion was studied in a representative higher primate, the rhesus monkey. As control against these two peptides, normal saline and a scrambled sequence of 26RFa was administered. A set of four intact adult male monkeys received the administration in a random order. Peripheral blood samples were obtained from the chairrestrained but fully conscious animals for a period of 30 min before and 240 min after the administration at 15-min intervals. For quantitative measurement of GH concentration, a human GH chemiluminescent immunometric assay was used. Peripheral administration of 38 and 76 nmol doses of 26RFa significantly (P < 0.05) stimulated GH AUC during a 0-120 min period after injection of 26RFa. In contrast to 26RFa, administration of 43RFa appeared to suppress GH levels during the later stages of the sampling i.e. from 120 to 240 min period. Mean AUC during the period was significantly (P < 0.05) reduced by 76 nmol dose of 43RFa, while 38 nmol dose of 43RFa also had similar effect but lacked full statistical significance (P = 0.058). To our knowledge present study reports for the first time-specific stimulatory effect of 26RFa on the GH secretion and a novel inhibitory and delayed effect of 43RFa on the GH secretion in higher primates. In conclusion, present findings extend evidence for endocrine actions of RF amides in primates and suggest differential effect of these peptides on GH secretion in primates.

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Fluvastatin's hepatoprotective impact is being investigated in the current study. It is possible that the oxidative stress pathway is implicated in PCM hepatotoxicity. The acute hepatotoxicity of PCM was investigated in this study. Place of study: Rashid Latif Medical College Lahore Materials and Methods: The rabbits were divided into five groups of ten each. The saline group received (the vehicle). Fluvastatin (20 mg/kg), PCM (600 mg/kg), and PCM + 10 mg Fluvastatin (600 mg PCM + 20 mg Fluvastatin) were administered to the animals. The livers from all the animals were taken out and cleansed. 70% alcohol was used for washing extensively, after which the liver tissue was embedded in paraffin and then 5 mm thick paraffin slices were stained by aid of hematoxylin and eosin. Results: Male rabbits were shown to be harmful to paracetamol (P<0.05). However, as compared to group 1, the levels of bilirubin, ALT, AST, and ALP were considerably higher (P<0.0001) (In the control group.) Fluvastatin (10mg/kg and 20mg/kg) combined with paracetamol resulted in significant reductions in ALP, ALT, and bilirubin levels.Slices of liver were analyzed histologically. Conclusion: Fluvastatin reduced the severity of all of these side effects, although it did not completely eliminate them. Keywords: Fluvastatin, Hepatotoxicity, Paracetamol, Hepato protection, histopathology.

Background:Lead harms haematological, biochemical, and hepatic parameters, hence studies have concentrated on antioxidants with therapeutic potentials. Objective: Induced hepatotoxicity and hemato-biochemical parameters in adult Wistar rats with Ocimum Gratissimum extract. Methodology: 42 adult Wistar rats were divided into seven groups of five. Group A was the control, Group B had 120 mg/kg lead, and Group C got 300 mg/kg OG. D and E had 120 mg/kg lead before 300 mg/kg and 600 mg/kg OG. Group F had 300 mg OG extract, then 120 mg lead, whereas Group G got 120 mg lead and 1000 mg ascorbic acid. The animals were then slaughtered and blood and liver tissues were taken for biochemical and histological investigation. Results: The outcome revealed a rise in Control but a drop in B. ALT, AST, GGT, and ALP levels were higher in Group B than in Control and other treatment groups (p≤ 0.05). As in Groups D, E, F, and G, histological investigation of liver tissues revealed degenerative alterations with localised necrosis and aggregated inflammatory cells in B. Conclusion: The extract of OG has the potential to be employed as a medicinal agent in the treatment of lead poisoning. Keywords: Hepatobiochemical; Lead; Liver; Ocimum gratissimum; Wistar rats; Parameters