Brain uptake of α-[14C]methyl-para-tyrosine in the rat

The blood-brain permeabilities of L-[³H]tyrosine and the tyrosine hydroxylase (TH) inhibitor β-[¹⁴C]methyl-para-tyrosine ([¹⁴C]AMPT) were determined in rat striatum, a brain region rich in TH activity, and in other brain regions containing relatively little TH activity. In striatum, the unidirectional clearance rate (K₁) for L-[³H]tyrosine (6.2 ml hg- ^?1 min^?1) was significantly greater than the rates for L-[¹⁴C]AMPT (2.8 ml hg^?1 min^?1) and D-[¹⁴C]AMPT (0.8 ml hg^?1 min^?1). The apparent volume of distribution (V_f) for L-[¹⁴C]AMPT in striatum (72.5 ± 4.0 ml hg-¹) did not differ from the V_f in other brain regions. The homogeneous distribution of L-[¹⁴C]AMPT in rat brain indicates that labeled AMPT is unsuitable for the study of TH in vivo by quantitative autoradiography. © 1994 Wiley-Liss, Inc.     

Lack of association of angiotensin I-converting enzyme gene polymorphism and premature myocardial infarction in Mauritian Indians

Eighty-five young Mauritian Indians, male survivors of premature myocardial infarction (MI) and thus belonging to a high risk group, were compared with 108 stringently selected controls for a possible association between premature MI and an insertion/deletion (I/D) polymorphism in the gene encoding angiotensin I-converting enzyme (ACE). The frequency of the D allele was 0.42 in the MI group and 0.43 in the control group, and thus no association between I/D polymorphism of ACE with susceptibility to early-onset MI was found in this population group. Other gene components of the renin-angiotensin system and lipid metabolism need to be explored to understand the genetic factors involved in causing MI at an early age.     

Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. We plan to use this method to synthesize indolizidine (−)-237D analogs to find α6-selective antismoking agents. Therefore, we also performed in silico α6-nAchRs binding studies of selected products. Compounds with low root-mean-square deviation values showed more favorable binding free energies. We also report preliminary pharmacokinetic data on indolizidine (−)-237D and found it to have weak activity at CYP3A4. In addition, as enamino carbonyl compounds are also known for antimicrobial properties, we screened previously reported and new enamino carbonyl compounds for antibacterial, antimicrobial, and antifungal properties. Eleven compounds showed significant antimicrobial activities.

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides.     

Correlation between clinical features and magnetic resonance imaging findings in lumbar disc prolapse

Background:

Lumbar disc prolapse is one of the common causes of low back pain seen in the working population. There are contradictorty reports regarding the clinical significance of various magnetic resonance imaging (MRI) findings observed in these patients. The study was conducted to correlate the abnormalities observed on MRI and clinical features of lumbar disc prolapse.

Materials and Methods:

119 clinically diagnosed patients with lumbar disc prolapse were included in the study. Clinical evaluation included pain distribution, neurological symptoms and signs. MR evaluation included grades of disc degeneration, type of herniation, neural foramen compromise, nerve root compression, and miscellaneous findings. These MRI findings were tested for inter- and intraobserver variability. The MRI findings were then correlated with clinical symptoms and the level of disc prolapse as well as neurological signs and symptoms. Statistical analysis included the Kappa coefficient, Odd’s ratio, and logistic regression analysis.

Results:

There were no significant inter- or intraobserver variations for most of MRI findings (Kappa value more than 0.5) except for type of disc herniation which showed a interobserver variation of 0.46 (Kappa value). The clinical level of pain distribution correlated well with the MRI level (Kappa 0.8), but not all disc bulges produced symptoms. Central bulges and disc protrusions with thecal sac compression were mostly asymptomatic, while centrolateral protrusions and extrusions with neural foramen compromise correlated well with the dermatomal distribution of pain. Root compression observed in MRI did not produce neurological symptoms or deficits in all patients but when deficits were present, they correlated well with the presence of root compression in MRI. Multiple level disc herniations with foramen compromise were strongly associated with the presence of neurological signs.

Conclusions:

The presence of centrolateral protrusion or extrusion with gross foramen compromise correlates with clinical signs and symptoms very well, while central bulges and disc protrusions correlate poorly with clinical signs and symptoms. The presence of neural foramen compromise is more important in determining the clinical signs and symptoms while type of disc herniation (bulge, protrusion, or extrusion) correlates poorly with clinical signs and symptoms.