Self-monitoring of blood pressure and the role of community pharmacists in Kuwait.

Objective: To determine the types of devices for self-monitoring of blood pressure available to consumers in Kuwait and the pharmacists' knowledge and level of information provided to consumers when purchasing such devices.

Materials And Methods: It was possible to contact 196 of the 230 eligible pharmacies from five governorates in Kuwait. Ten of these were used to pretest the questionnaire and six declined to participate.

Role of protein kinase C in substance P-induced synaptic depression in the nucleus accumbens in vitro.

Objectives: This study set out to determine the roles of protein kinase A (PKA) and protein kinase C (PKC) signalling cascades in substance P- (SP-) mediated synaptic depression in the nucleus accumbens.

Materials And Methods: We used whole-cell patch recording in rat forebrain slices to study the effects of excitatory and inhibitory modulators of PKA and PKC to determine their effects on SP-induced synaptic depression.

Results: We showed that cAMP and PKC, but not PKA, are involved in SP-induced synaptic depression.

Cholecystokinin-2 receptors couple to cAMP-protein kinase A to depress excitatory synaptic currents in rat nucleus accumbens in vitro.

We recently reported that the activation of cholecystokinin-2 receptors depress evoked excitatory postsynaptic currents (EPSCs) in nucleus accumbens (NAc) indirectly through gamma-aminobutyric acid (GABA) acting on gamma-aminobutyric acid-B (GABA(B)) receptors. Here, we determined the second messenger system that couples cholecystokinin-2 receptors to the observed synaptic depression. Using in vitro forebrain slices of rats and whole-cell patch recording, we tested the hypothesis that cholecystokinin-2 receptors are coupled to cAMP and protein kinase A signaling pathway.

Practice and opinion towards disposal of unused medication in Kuwait.

Objectives: The aim of this study was to measure the attitude and practice of Kuwaiti patients in Kuwait with regard to safe disposal of unwanted medicines.

Subjects And Methods: Three-hundred patients or their family members waiting for prescriptions at public general hospitals in Kuwait completed a questionnaire soliciting their practice with regard to medication use and disposal, and their opinion of the best way to dispose of unwanted medicines.

Results: Almost half of the respondents (45.

Cholecystokinin inhibits evoked inhibitory postsynaptic currents in the rat nucleus accumbens indirectly through gamma-aminobutyric acid and gamma-aminobutyric acid type B receptors.

We recently reported that cholecystokinin (CCK) excited nucleus accumbens (NAc) cells and depressed excitatory synaptic transmission indirectly through gamma-aminobutyric acid (GABA), acting on presynaptic GABAB receptors (Kombian et al. [2004] J. Physiol.

Cholecystokinin activates CCKB receptors to excite cells and depress EPSCs in the rat rostral nucleus accumbens in vitro.

The peptide cholecystokinin (CCK) is abundant in the rat nucleus accumbens (NAc). Although it is colocalized with dopamine (DA) in afferent terminals in this region, neurochemical and behavioural reports are equally divided as to whether CCK enhances or diminishes DA's actions in this nucleus. To better understand the role of this peptide in the physiology of the NAc, we examined the effects of CCK on excitatory synaptic transmission and tested whether these are dependent on DA and/or other neuromodulators.

Dopamine and adenosine mediate substance P-induced depression of evoked IPSCs in the rat nucleus accumbens in vitro.

The major projection cells of the nucleus accumbens (NAc) are under a strong inhibitory influence from GABAergic afferents and depend on afferent excitation to produce their output. We have earlier reported that substance P (SP), a peptide which is colocalized with GABA in these neurons, depresses excitatory synaptic transmission in this nucleus (Kombian, S.B.

Substance P depresses excitatory synaptic transmission in the nucleus accumbens through dopaminergic and purinergic mechanisms.

Substance P (SP) is an undecapeptide that is co-localized with conventional transmitters in the nucleus accumbens (NAc). Its neurochemical and behavioral effects resemble those of cocaine and amphetamine. How SP accomplishes these effects is not known, partly because its cellular and synaptic effects are not well characterized.

Antibacterial agents: patent highlights January to June 2002.

A total of 48 patents dealing with disclosures on the different classes of antibacterial agents, including the beta-lactams, oxazolidinones, macrolides, quinolones, tetracyclines and miscellaneous antibacterial agents reported between January and June 2002 are selected for review. The miscellaneous agents section focused on the significant discovery of potential lead compounds as inhibitors of bacterial fatty acid synthase and peptide deformylase, and also included examples of novel peptidic antibiotics and pleuromutilin derivatives along with their antibacterial activities. Only a few patents disclosed novel agents in the quinolone and carbapenem areas.

Ultraviolet spectroscopy of anticonvulsant enaminones.

The ultraviolet (UV) spectra of selected enaminones were determined in acidic, alkaline and neutral media and compared to their anticonvulsant activities. The wavelength of maximum absorption and molar absorptivity were compared with the anticonvulsant activity of the selected secondary and tertiary enaminones, and general inferences were made. The UV spectra of the enaminones had hypsochromic shifts in acidic media in comparison with neutral media.

GABA(B) receptors modulate short-term potentiation of spontaneous excitatory postsynaptic currents in the rat supraoptic nucleus in vitro.

High-frequency stimulation of afferents to the supraoptic nucleus (SON) results in a robust increase in the frequency and amplitude of pharmacologically isolated, tetrodotoxin-resistant, miniature excitatory postsynaptic currents (mEPSCs) lasting for 5-20 min. This increase in mEPSC frequency, termed short-term potentiation (STP), is tightly coupled to increases in action potential firing in magnocellular neurons (MCNs) suggesting a functional role for STP. gamma-Aminobutyric acid (GABA), acting selectively on GABA(B) receptors, has been shown to modulate action potential-dependent EPSCs, as well as mEPSCs in this nucleus.

Antibacterial agents (oxazolidinones, quinolones, macrolides and new agents): patent highlights June to December 2000.

Several patent disclosures were made on oxazolidinone, quinolone, macrolide and new antimicrobial agents between June and December 2000; 26 of these patents are discussed in this review. The exciting report on new oxazolidinone derivatives with potent activity against fastidious Gram-negative organisms is highlighted. Most of the new quinolones are structurally dissimilar to the traditional fluoroquinolones and demonstrate activity against Helicobacter pylori (MIC=0.

Synthesis and calcium channel antagonist activity of dialkyl 1,4-dihydro-2,6-dimethyl-4-[4-(1-methoxycarbonyl-1,4-dihydropyridyl)]-3 ,5- pyridinedicarboxylates.

A novel class of dialkyl 1,4-dihydro-2,6-dimethyl-4-[4-(1- methoxycarbonyl-1,4-dihydropyridyl)]-3,5-pyridinedicarboxylates (8-14) were synthesized and evaluated as calcium channel antagonists. The differences in activity among members of this new class of compounds was less than one log unit (IC50 range of 1.12 x 10(-6) to 8.

Adrenergic regulation of translocation of protein kinase C isozymes in rat pinealocytes.

Protein kinase C (PKC) is involved in the alpha1-adrenergic-potentiation of beta-adrenergic stimulated cyclic nucleotide responses in rat pinealocytes. In the present study, the PKC isozymes expressed in rat pinealocytes and their regulation by norepinephrine (NE) were investigated. Western blot analysis identified PKC alpha (a classical PKC isozyme), PKC delta and epsilon (novel PKC isozymes), and PKC zeta: (atypical PKC isozymes).

Synthesis, rotamer orientation, and calcium channel modulation activities of alkyl and 2-phenethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3- or 6-substituted-2-pyridyl)-5-pyridinecarboxylates.

A group of racemic alkyl and 2-phenethyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3- or 6-substituted-2-pyridyl)-5-pyridinecarboxylates (13a-q) was prepared using a modified Hantzsch reaction that involved the condensation of a 3- or 6-substituted-2-pyridinecarboxaldehyde (7a-j) with an alkyl or 2-phenethyl 3-aminocrotonate (11a-d) and nitroacetone (12). Nuclear Overhauser (NOE) studies indicated there is a significant rotamer fraction in solution where the pyridyl nitrogen is oriented above the 1,4-dihydropyridine ring, irrespective of whether a substituent is located at the 3- or 6-position. A potential H-bonding interaction between the pyridyl nitrogen free electron pair and the suitably positioned 1,4-dihydropyridine NH moiety may stablize this rotamer orientation.

Synthesis and calcium channel-modulating effects of alkyl (or cycloalkyl) 1,4-dihydro-2,6-dimethyl-3-nitro-4-pyridyl-5-pyridinecarboxylate racemates and enantiomers.

A group of racemic alkyl (or cycloalkyl) 1,4-dihydro-2,6- dimethyl-3-nitro-4-(2-, 3-, or 4-pyridyl)-5-pyridinecarboxylate isomers (6-14) were prepared using a modified Hantzsch reaction that involved the condensation of nitroacetone with an alkyl (or cycloalkyl) 3-aminocrotonate and 2-, 3-, or 4-pyridinecarboxaldehyde. Determination of their in vitro calcium channel-modulating activities using guinea pig ileum longitudinal smooth muscle (GPILSM) and guinea pig left atrium (GPLA) assays showed that the 2-pyridyl isomers acted as dual cardioselective calcium channel agonists (GPLA)/smooth muscle selective calcium channel antagonists (GPILSM). In contrast, the 3-pyridyl and 4-pyridyl isomers acted as calcium channel agonists on both GPLA and GPILSM.

Activation of phospholipase D in FRTL-5 thyroid cells by forskolin and dibutyryl-cyclic adenosine monophosphate.

We demonstrated previously that TSH activates phospholipase D (PLD) via stimulation of protein kinase C (PKC) in Fischer rat thyroid line (FRTL)-5 thyroid cells. To examine the role of the cAMP pathway in the regulation of PLD, we studied the effects of forskolin (0-100 microM; 30 min) and dibutyryl cAMP (dbcAMP; 0-1 mM; 30 min) on PLD activation. FRTL-5 thyroid cells were labeled mainly in phosphatidylcholine with [3H]myristate followed by incubation with 200 mM ethanol before the addition of agonist.

Effects of the diacylglycerol kinase inhibitor, R59022, on TSH-stimulated iodide organification in porcine thyroid cells.

We and others have demonstrated that protein kinase C (PKC) activators such as the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), inhibit differentiated thyroid function in vitro. However, phorbol-mediated PKC activation differs from that induced by analogues of the endogenous PKC activator, diacylglycerol (DAG). To explore the effects of endogenous PKC activation on differentiated thyroid function, we examined the effects of the DAG kinase inhibitor, R59022, on TSH-mediated iodide organification in porcine thyroid cells.

Regulation of protein kinase C isoforms in FRTL-5 thyroid cells by TSH and phorbol ester.

Activation of protein kinase C (PKC) has been observed following TSH exposure in FRTL-5 thyroid cells. However, PKC exists as a family of isoforms displaying individual characteristics. Recently, Wang et al.

Thyroid-stimulating hormone activates phospholipase D in FRTL-5 thyroid cells via stimulation of protein kinase C.

We studied whether TSH or phorbol myristate acetate (PMA) stimulates the hydrolysis of phospholipids, predominantly phosphatidylcholine, via phospholipase D (PLD) in FRTL-5 thyroid cells and whether this occurs as a consequence of protein kinase C (PKC) activation. FRTL-5 thyroid cells were labeled with [3H]myristate followed by incubation with 200 mM ethanol before the addition of agonist. PLD activity was assessed by the measurement of [3H]phosphatidylethanol from [3H]phospholipid (predominantly [3H]phosphatidylcholine).

Syntheses, calcium channel agonist-antagonist modulation activities, and voltage-clamp studies of isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-pyridinylpyridine-5-carboxylate racemates and enantiomers.

A novel group of racemic isopropyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-pyridinylpyridine-5-carboxylate isomers [(+/-)-12-14] were prepared using a modified Hantzsch reaction that involved the condensation of nitroacetone with isopropyl 3-aminocrotonate and 2-, 3-, or 4-pyridinecarboxaldehyde. Determination of their in vitro calcium channel-modulating activities using guinea pig ileum longitudinal smooth muscle (GPILSM) and guinea pig left atrium (GPLA) assays showed that the 2-pyridinyl isomer (+/-)-12 acted as a dual cardioselective calcium channel agonist (GPLA)/smooth muscle selective calcium channel antagonist (GPILSM). In contrast, the 3-pyridinyl [(+/-)-13] and 4-pyridinyl [(+/-)-14] isomers acted as calcium channel agonists on both GPLA and GPILSM.

Increased membrane-bound protein kinase C in porcine thyroid cells following TSH exposure.

Activation of protein kinase C (PKC) follows its translocation from the cytosol to an active membrane-bound form. Previously, we demonstrated that only high concentrations of partially-purified bovine thyroid-stimulating hormone (TSH) could translocate PKC in vitro when measured by histone phosphorylation. Measuring PKC by Western blotting, we assessed whether physiological concentrations of human TSH could translocate PKC in porcine thyroid cells.

Downregulation of protein kinase C levels leads to inhibition of GnRH-stimulated gonadotropin secretion from dispersed pituitary cells of goldfish.

We have previously shown that the abilities of the two native goldfish GnRHs, salmon GnRH (sGnRH) and chicken GnRH II (cGnRH II), to stimulate gonadotropin (GtH) secretion and elevate intracellular Ca2+ levels are mimicked by the protein kinase C (PKC) stimulators, 1,2-dioctanoylglycerol (DiC8) and 12-O-tetradecanoyl phorbol-13-acetate (TPA). The ability of PKC inhibitors to attenuate GnRH-stimulated GtH secretion was also demonstrated. In the present study, the involvement of PKC was examined through the reduction of cellular PKC levels by prolonged preincubation of the cells with TPA (TPA desensitization).

Enhancement of thyrotropin-stimulated iodide organification in porcine thyroid cells after protein kinase-C inhibition.

We and others have previously shown that 12-O-tetracanoylphorbol-13-acetate (TPA), a protein kinase-C (PKC) activator, inhibits TSH-stimulated iodide organification in porcine thyroid cells. However, TPA action may be independent of PKC. To further explore the role of PKC in the regulation of differentiated thyroid function, we studied the effects of the PKC inhibitors 1-O-hexadecyl-2-O-methylglycerol (AMG-C16), 1-(5-isoquinolinesulfonyl)2-methylpiperazine (H7), and staurosporine on TSH-stimulated iodide organification in porcine thyroid cells in the presence and absence of TPA.

Synthesis and calcium channel antagonist activity of dialkyl 1,4-dihydro-2,6-dimethyl-4-[3-(1-methoxy-carbonyl-4-substituted-1,4- dihydro-pyridyl)]-3,5-pyridinedicarboxylates.

A novel class of dialkyl 1,4-dihydro-2,6-dimethyl-4-(3-[1- methoxycarbonyl-4-(H, Me, n-Bu or Ph)-1,4-dihydropyridyl])-3,5-pyridinedicarboxylates (3-29) were synthesized and evaluated as calcium channel antagonists using the muscarinic receptor mediated Ca2+ dependent contraction of guinea pig ileal longitudinal smooth muscle (GPILSM). The differences in activity among members of this new class of compounds was less than one log unit (IC50 range of 8.25 x 10(-6) to 4.