Studies of the mechanism of drug clearance: with special reference to the clearance of humoral agents

1. Continuous infusion of adrenaline in the cat produces over a wide range of doses a plateau response both in the nictitating membrane and blood pressure.2. This indicates that enzyme saturation does not occur even with large doses (correction of conclusion of Clark and Raventos, 19394).3. The relation between the continuous and equivalent quick dosage shored that the amount cleared per minute varied as (concentration present)²/³.4. Such a form of clearance was also found by dosage- duration relation as it showed a linear relation between (dose)¹/³ and the duration of action.5. The mathematical calculations of the course of cumulation and clearance of adrenaline made by means of the formulae derived from the above relation approximate with the observed results.6. Mathematical methods calculating the clearance of adrenaline from its pharmacological effects on the blood pressure and nictitating membrane of cat have been used to study the effects of drugs which inhibit its destruction.7. The rate of clearance of adrenaline calculated was diminished to about 40 per cent. by pyrogallol and to 55 per cent. by cocaine, but was not affected by ascorbic acid.8. Large doses of cocaine inhibited the effect of large doses of adrenaline on the nictitating membrane.9. None of the enzyme inhibitors tested altered the relation found, i.e. continuous dose of adrenaline varies as (quick dose)¹/³.10. The failure of ascorbic acid to prolong the action of adrenaline was not due to its destruction, since its presence in the tissues in adequate concentration (0.15 per cent.) was demonstrated chemically

DALK (MASSAGE) AND ITS IMPLICATION IN THERAPY ACCORDING TO UNANI SYSTEM OF MEDICINE: A REVIEW

According to classical literature of Unani Medicine, management of any disease depends upon the diagnosis of disease. In the diagnosis, clinical features, i.e., signs, symptoms, laboratory investigations and Mizaj (temperament) are important. Any cause or factor is countered by Quwwat Mudabbira lil-Badan (medicatrix naturae: the power of body responsible to maintain health), the failing of which may lead to quantitatively or qualitatively derangement of the normal equilibrium of Akhlat (humors) of body which constitute the tissues and organs. After diagnosing the disease, Usul-e-Ilaj (principle of treatment) of disease is determined on the basis of etiology. The principle of management is decided which may be one or more of the four types of treatment lines such as Ilaj bil-Tadbeer (Regimental therapy), Ilaj bil-Ghiza (Diet therapy), Ilaj bil-Dawa (Pharmacotherapy), Ilaj bil-Yad or Jarahat (Surgery). Ilaj bil-Tadbeer is most preferred one. Dalk is one of the most important parts of Ilaj bil-Tadbeer. Details about Dalk have been mentioned in Unani Literature, some of them are described in this paper

Iridium complexes bearing a PNP ligand, favoring facile C(sp^3)–H bond cleavage

Hydrogen iodide is lost upon reaction of PNP with IrI_3, where PNP = 2,6-bis-(di-t-butylphosphinomethyl)pyridine to give crystallographically characterized Ir(PNP)*(I)_2, which reacts with H_2 to give Ir(PNP)(H)(I)_2. Ir(PNP)(Cl)_3 is relatively inert towards the intramolecular C–H activation of the tert-butyl's of the PNP ligand

Acceleration of Nucleophilic CH Activation by Strongly Basic Solvents

(IPI)Ru(II)(OH)_n(H_2O)_m, 2, where IPI is the NNN-pincer ligand, 2,6-diimidizoylpyridine, is shown to catalyze H/D exchange between hydrocarbons and strongly basic solvents at higher rates than in the case of the solvent alone. Significantly, catalysis by 2 is accelerated rather than inhibited by increasing solvent basicity. The evidence is consistent with the reaction proceeding by base modulated nucleophilic CH activation

Crystal structure of Li_2B_(12)H_(12): a possible intermediate species in the decomposition of LiBH_4

The crystal structure of solvent-free Li_2B_(12)H_(12) has been determined by powder X-ray diffraction and confirmed by a combination of neutron vibrational spectroscopy and first-principles calculations. This compound is a possible intermediate in the dehydrogenation of LiBH_4, and its structural characterization is crucial for understanding the decomposition and regeneration of LiBH_4. Our results reveal that the structure of Li_2B_(12)H_(12) differs from other known alkali-metal (K, Rb, and Cs) derivatives

Impact of heart failure on stroke mortality and recurrence

Objective We aimed to examine the impact of heart failure (HF) on stroke mortality (in-hospital and postdischarge) and recurrence in a national stroke cohort from Thailand. Methods We used a large, insurance-based database including all stroke admissions in the public health sector in Thailand between 2004 and 2015. Logistic and Royston-Parmar regressions were used to quantify the effect of HF on in-hospital and long-Term outcomes, respectively. All models were adjusted for age, sex and comorbidities and stratified by stroke type: Acute ischaemic stroke (AIS) or intracerebral haemorrhage (ICH). Multistate models were constructed using flexible survival techniques to predict the impact of HF on the disease course of a patient with stroke (baseline-[recurrence]-death). Only first-ever cases of AIS or ICH were included in the multistate analysis. Results 608 890 patients (mean age 64.29±13.72 years, 55.07% men) were hospitalised (370 527 AIS, 173 236 ICH and 65 127 undetermined pathology). There were 398 663 patients with first-ever AIS and ICH. Patients were followed up for a median (95% CI) of 4.47 years (4.45 to 4.49). HF was associated with an increase in postdischarge mortality in AIS (HR [99% CI] 1.69 [1.64 to 1.74]) and ICH (2.59 [2.07 to 3.26]). HF was not associated with AIS recurrence, while ICH recurrence was only significantly increased within the first 3 years after discharge (1.79 [1.18 to 2.73]). Conclusions HF increases the risk of mortality in both AIS and ICH. We are the first to report on high-risk periods of stroke recurrence in patients with HF with ICH. Specific targeted risk reduction strategies may have significant clinical impact for mortality and recurrence in stroke

Location of a 4-coordinate H atom via neutron diffraction

n/

Remediation of the protein data bank archive

The Worldwide Protein Data Bank (wwPDB; wwpdb.org) is the international collaboration that manages the deposition, processing and distribution of the PDB archive. The online PDB archive at ftp://ftp.wwpdb.org is the repository for the coordinates and related information for more than 47 000 structures, including proteins, nucleic acids and large macromolecular complexes that have been determined using X-ray crystallography, NMR and electron microscopy techniques. The members of the wwPDB–RCSB PDB (USA), MSD-EBI (Europe), PDBj (Japan) and BMRB (USA)–have remediated this archive to address inconsistencies that have been introduced over the years. The scope and methods used in this project are presented