Enhancing CO2 Capture via Metal-Ligand Cooperativity: Tuning Ligand Basicity and Zn(II) Lewis Acidity.

A series of thiosemicarbazonato-hydrazinatopyridine zinc(II) complexes were evaluated as direct air CO2 capture agents. The complexes sequester CO2 in a methanol solution as a metal-coordinated methylcarbonate. The reaction is reversible upon sparging of solutions with an inert gas (N2 or Ar). The capture process involves metal-ligand cooperativity with the noncoordinating nitrogen of the hydrazinatopyridine functional group serving as a Brønsted-Lowry base and the zinc acting as a Lewis acid. In this study, the pendent amine of the thiosemicarbazonato group was varied to include 4-phenyl (ZnL5), 4-(trifluoromethyl)phenyl (ZnL6), 4-cyanophenyl (ZnL7), 4-tolyl (ZnL8), and 4-naphthyl (ZnL9). Hyperconjugation between the pendent group and the ligand core resulted in modulation of the metal ion acidity, as quantified by ligand exchange equilibrium constants (K3 = 193-511) and ligand basicity (pKa,MeOH = 11.09-11.94). Variations in electronic structure that decreased ligand basicity were more than offset by increases in Lewis acidity. The equilibrium constant (K1) for CO2 capture varied from 46300 to 73700. Overall, the value of K1 was directly related to the relative Lewis acidity of the complexes (K3). Notably, there was an overall inverse relationship between K1 and the ligand basicity. The results provide insights into ligand design to further improve CO2 capture.

Treating Philadelphia chromosome/BCR-ABL1 positive patients with Glivec (Imatinib mesylate): 10 years' experience at Patan Hospital, Nepal.

The Glivec International Patient Assistance Programme makes Glivec (Imatinib mesylate) available to Philadelphia chromosome/BCR-ABL1 positive patients with chronic myeloid leukaemia (CML) in Lower and Middle Income Countries (LMIC). We have established a large cohort of 211 CML patients who are eligible for Imatinib, in Kathmandu, Nepal. Thirty-one patients were lost to follow-up. We report on 180 CML patients with a median age of 38 years (range 9-81). Of these 180 patients, 162 underwent cytogenetic testing and 110 were investigated by reverse transcription polymerase chain reaction. One hundred and thirty-nine of the 180 patients (77·2%) had at least one optimal response. Taken together, our cohort has a 95% overall survival rate and 78% of the patients were still taking Glivec at a median time of 48·8 months (range 3-140 months). The number of patients who actually failed therapy, as defined by the LeukaemiaNet 2013 criteria, was 39 (21·7%). While our cohort has some differences with those in North America or Europe, we have shown Glivec is effective in inducing an optimal response in our patients in Nepal and that it is possible to deliver a clinical service for CML patients using tyrosine kinase inhibitors in resource-poor settings.

The use of Imatinib resistance mutation analysis to direct therapy in Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia patients failing Imatinib treatment, in Patan Hospital, Nepal.

Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia (CML) can be successfully treated with Glivec (Imatinib), which is available free of cost through the Glivec International Patient Assistance programme (GIPAP) to patients with proven CML without means to pay for the drug. We review the acquired mutations in the tyrosine kinase encoded by the BCR-ABL1 gene underlying Glivec failure or resistance in a cohort of 388 imatinib-treated CML patients (149 Female and 239 male) registered between February 2003 and June 2016 in Nepal. Forty-five patients (11 female 34 male) were studied; 18 different BCR-ABL1 mutations were seen in 33 patients. P-loop mutation, Kinase domain and A-loop mutations were seen in 9, 16 and 4 patients respectively. Other mutations were seen in five patients. A T315I mutation was the most common mutation, followed by F359V and M244V. Sixteen mutations showed intermediate activity to complete resistance to Glivec. Among the 45 patients evaluated for BCR-ABL1 mutations, 4 were lost to follow-up, 14 died and 27 are still alive. Among the surviving patients, 16 are receiving Nilotinib, 5 Dasatinib and 3 Ponatinib, while 3 patients were referred to India, one of who received allogenic bone marrow transplantation. Understanding the spectrum of further acquired mutations in BCR-ABL1 may help to choose more specific targeted tyrosine kinase inhibitors that can be provided by GIPAP.

Intravenous Ringers lactate versus normal saline for predominantly mild acute pancreatitis in a Nepalese Tertiary Hospital.

BACKGROUND: Acute pancreatitis (AP) is a common presentation in patients admitted with acute abdomen. Whether Ringers lactate (RL) or Normal Saline (NS) as a resuscitation fluid is better still remains unclear. The aim of this study is to compare the efficacy of RL and NS in terms of control of systemic inflammation by measuring indirect markers specifically Systemic Inflammation Response Syndrome (SIRS) scores and C- Reactive Protein (CRP) level. METHODS: This was an open label randomized trial conducted in a tertiary level hospital of Nepal. Ethical approval was obtained prior to the study. Patients with acute pancreatitis were randomized to either RL or NS group for the fluid resuscitation. The fluid was given as per the study protocol for three days for hydration. Baseline SIRS and CRP were recorded on admission and subsequently as defined. All the data were analyzed using SPSS ver 20.0 software. RESULTS: Total 51 patients were enrolled, 26 in RL and 25 in NS group. The commonest etiology of AP was alcohol (84.31%). SIRS was present in 46.2% and 64.0% of patients in RL and NS group respectively (p = 0.20) on admission. At least one SIRS criteria was still present in 44.0% of patients in the NS group compared to only 15.4% in the RL group after 24 hours (p = 0.025). The baseline CRP were comparable in both the groups. However after 72 hours, the increment of CRP was more in the NS group compared to the RL group; median value of 14.2 mg/dl (12.15, 16.45) and 22.2 mg/dl (18.20, 30.60) in RL and NS group respectively (p<0.001). CONCLUSIONS: Ringers lactate was associated with a reduction in systemic inflammation compared to normal saline in patients with acute pancreatitis. Incidence of SIRS at 72 hours and occurrence of local complications were however similar in both the groups.

Correlation of Central with Jugular and Upper-limb Venous Pressure Measurements.

BACKGROUND: Correlation data of different external reference points and methods used to measure venous pressures are scarce in the literature. We correlated central venous pressure with jugular venous pressure measured from sternal angle and with jugular and upper-limb venous pressures from zero level corresponding to mid-right-atrium level. METHODS: A hospital-based observational study in the medical and surgical intensive care units was conducted for period of one year. Central venous pressure was measured from right fourth intercostal space in mid-axillary line and jugular venous pressure from sternal angle and jugular and upper-limb venous pressures from horizontal plane through the midpoint of anteroposterior line from anterior end of right fourth intercostal space to back. We measured central venous pressure by central venous cannulation and jugular and upper-limb venous pressures clinically by JVP Meter®. Upper-limb venous pressure was indicated by collapse of visible veins in dorsum of hands as the arm was slowly raised from dependent position. RESULTS: Correlation coefficient (r) values were 0.61 between central venous pressure and jugular venous pressure from zero level, 0.48 between central venous pressure and jugular venous pressure from sternal angle, and 0.31 between central and upper-limb venous pressures; and 0.67 and 0.50 between central venous pressure measured from right internal jugular vein and jugular venous pressure from zero level and sternal angle respectively and 0.52 and 0.44 between central venous pressure from right sub-clavian vein and jugular venous pressure from zero level and sternal angle respectively. CONCLUSIONS: Different correlation values indicate the need to have future investigations and consensus on the common external reference point and methods to measure venous pressures.