Conformational and Electrostatic Properties of Naphthazarin, Juglone, and Naphthoquinone: An Ab Initio Theoretical Study

Conformational features of naphthazarin, juglone, and naphthoquinone have been examined via ab initio (Hartree-Fock) SCF calculations at 3-21G level. The results suggest a planar structure for all the three molecules and internally hydrogen-bonded structure for naphthazarin and juglone to be their preferred conformation. The optimized structural features are essentially the same as their crystal geometries. Molecular electrostatic potential (MEP) calculations using ab initio SCF methods ranging from 3-21G to 6-31G levels have been performed to visualize their three-dimensional pharmacophoric patterns and topography. The results indicate that two factors-(1) the depth, extent, and relative location of negative potential around hydroxyl and quinonoid oxygens, and (ii) a gradual loss of negative potential over the molecular plane due to the presence and orientation of the hydroxyl groups in the phenolic part of the molecules-are crucial for recognition interaction of the compounds with their receptors. Aqueous solvation seems to have significant influence on the MEP profiles of the molecules. Although intrinsic nucleophilicity increases for all the compounds, including the different conformers, due to aqueous solvation, the intrinsic electrophilicity shows remarkable decrease for all. It appears that the acidic nature of the hydrogens in these compounds and conformers decreases sharply along with shifts of positions while going from the gas phase to the aqueous phase. These observations may help to explain the mechanism ofaction(s) of the anthracyclin family of cytotoxic antibiotics.     

A general hospital psychiatric unit inpatient facility

Summary Patients admitted to the inpatient ward of a psychiatric unit in a general hospital have been studied with regard to their clinical characteristics, reasons for admission and discharge patterns. The results indicate that patients are most often admitted for the management of acute disturbance and detailed diagnostic evaluation and they are discharged in a semi-improved state. Implications of such a service pattern are discussed.     

Stimulus-controlled delivery of drugs and genes

Macromolecular and colloidal systems used for the systemic delivery of drugs and genes promise to improve the way we treat and prevent numerous diseases. New generations of drug and gene delivery systems (DGDS) are being designed to enhance further efficiency by using a range of endogenous and external stimuli. This review focuses on three qualitatively distinct ways a stimulus can improve the efficiency of DGDS; namely, by selectively triggering release of the therapeutic agent from the DGDS, by modulating physical properties of DGDS and by favourably altering physiological properties of tissues to enhance DGDS transport. Recent developments in these areas are discussed to illustrate the potential of stimulus-controlled DGDS in the development of new generations of therapeutics.     

Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial

Aim: To compare the incidence of hyponatremia in full‐term neonates with severe hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5% dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET). Methods: In this double‐blind, randomized, controlled trial, full ‐ term newborns (≥37 weeks), appropriate for gestational age, with severe non‐haemolytic hyperbilirubinemia (serum bilirubin ≥ 20 mg/dL) were enrolled. Eligible neonates were randomized to receive either 0.2% saline in 5% dextrose (hypotonic fluid group) or 0.9% saline in 5% dextrose (isotonic fluid group) over 8 hrs, in addition to phototherapy. The primary outcome was proportion of neonates developing hyponatremia (serum Na < 135 mmol/L) after 8 h. Results: Forty‐two neonates were analysed in each group. Proportion of neonates developing hyponatremia after 8 h was higher in hypotonic fluid group as compared to isotonic fluid group (48.8% vs. 10.5%, p < 0.001). However, a larger proportion in isotonic fluid group developed hypernatremia (39.5% vs. 12.2%, p < 0.001). The rate of BET was similar in both groups. Conclusion: In full‐term neonates with severe hyperbilirubinemia, administration of hypotonic fluid to prevent BET was associated with a higher incidence of hyponatremia while isotonic fluid was associated with an increased incidence of hypernatremia.     

Nucleotide deletion in RHCE*cE (907delC) is responsible for a D- - haplotype in Hispanics

BACKGROUND: Lack of Cc and Ee expression is associated with either hybrid alleles in which regions of RHCE are replaced by RHD or nucleotide deletion(s) in RHCE. The former have been found as D– – phenotypes, and the latter as Rh_null when accompanied by deletion of RHD. We investigated RH in eight samples, three presenting as D– –, whose c–E– red blood cell (RBC) typing was discordant with the RHCE genotype that predicted c+E+. STUDY DESIGN AND METHODS: Serologic and molecular testing was performed by standard methods. CASES AND RESULTS: RBCs from Patient 1 were D+C?E?c+e+^w but DNA testing predicted E+. RBCs from Patients 2, 3, and 4 typed as D+C?E?c?e? but DNA testing predicted c+E+. All had alloantibodies strongly reactive with all RBCs tested except D– – and Rh_null. Patient 5 had anti‐c and anti‐E but DNA testing predicted she was c+E+. RBCs from three donors typed D+C+E?c?e+ with DNA testing predicting c+E+. All had RHCE*cE with deletion of nucleotide 907C in Exon 6 predicted to cause a premature stop codon at Amino Acid 303 (Leu303Stop). HphI polymerase chain reaction–restriction fragment length polymorphism was used to confirm the deletion and to screen 100 Hispanic, 100 Caucasian, and 100 African American donor samples. One additional example was found. CONCLUSIONS: A novel allele, RHCE*cE 907delC (ISBT provisional designation RHCE*03N.02), silences c and E and in the homozygous state resulted in a D– – phenotype and production of anti‐Rh17. All eight probands were Hispanic. The allele is associated with discrepant molecular typing, with an approximate frequency of 0.005 in Hispanics.