Fixed-dose combination therapy in the United States, Britain and Israel.

BACKGROUND: Fixed dose combination therapy varies among countries. OBJECTIVE: To compare the list of fixed-dose combination therapies used in the USA, UK and Israel. METHODS: The total list of drugs and FDC drugs were counted manually from a list of generic names. We also counted the number of drugs in four characteristic subgroups: cardiovascular, anti-infective, gastrointestinal, and dermatological. Data for drugs in the USA, UK and Israel were taken from the Physician's Desk Reference (PDR 1997), the British National Formulary (BNF March 1997) and the Monthly Ethical Drug Indexed Compilation (MEDIC July 1997) respectively. RESULTS: The global percentage of FDC drugs in the USA and UK was higher than in Israel (20%, 25% and 15% respectively). A similar trend was found in all subclasses of FDC drugs except for the anti-infective category in which the percentage of FDC drugs was low and similar in all countries. CONCLUSION: The list of FDC drugs varies greatly between the USA, UK and Israel, reflecting the differences in the outcome of debate between the pharmaceutical companies and the regulatory authorities.

Patterns of superficial fibre formation in the European pearlfish (Rutilus frisii meidingeri) provide a general template for slow muscle development in teleost fish.

The debate about the pattern of muscle formation in teleost fish has recently been heightened in the literature. Here we examine superficial muscle development in the pearlfish, a cyprinid endemic to a small area of Central Europe, and uninfluenced by economic interest and breeding. Using light and electron microscopy, histochemistry and immunohistochemistry techniques, we report that: (1) Superficial fibre precursors originate close to the notochord, are part of the same cell population as the so-called muscle pioneer cells, and are transferred laterally to end up at the surface of the myotome. (2) Superficial fibre maturation is exceptionally rapid. Structural and enzymatic functionality is attained at a time when prospective deep fibres have not passed beyond the early myotube state. This strong contrast weakens as the embryo develops. (3) Apart from the muscle pioneers, the superficial fibres appear to be capable of functioning before they receive any direct innervation, implying that signals are transferred to these fibres via cell-to-cell junctions. We suggest that the capability of rapid superficial fibre maturation is a rather general feature among teleosts and may aid pre-hatch survival under a variable environment. Our results indicate that muscle formation in teleost fish may follow a common basic pattern that is open to considerable ontogenetic and phylogenetic modification in response to habitat conditions.

Evidence for an endogenous clock in the retina of rainbow trout: II. Circadian rhythmicity of serotonin metabolism.

The purpose of the present study was to investigate patterns of circadian rhythmicity in the retina of a salmonid fish, the rainbow trout (Oncorhynchus mykiss). Our data present the first demonstration of intraretinal variations of serotonergic substances under light/dark-conditions (LD) and during continuous darkness (DD). All substances examined (serotonin, N-acetyl serotonin, 5-hydroxytryptophol, 5-hydroxyindole acetic acid) were rhythmic in LD. Serotonin, N-acetyl-serotonin, and 5-hydroxyindole acetic acid showed a preservation of specific features of rhythmicity in DD indicating the involvement of an endogenous pacemaker in the regulation of serotonin metabolism in the rainbow trout eye.

Evidence for an endogenous clock in the retina of rainbow trout: I. Retinomotor movements, dopamine and melatonin.

The purpose of the present study was to investigate patterns of circadian rhythmicity in the retina of a salmonid fish, the rainbow trout (Oncorhynchus mykiss). In a first attempt to show both morphological and neurochemical variations during light/dark conditions (LD) and during continuous darkness (DD), we investigated retinomotor movements and the associated regulatory transmitters, dopamine and melatonin. All parameters studied showed patterns of rhythmicity in LD and DD, clearly indicating the presence of an endogenous clock in the rainbow trout eye. The most salient variations of all parameters studied were found at the transitions from light to dark and vice versa in LD and from subjective day to subjective night and vice versa in DD. The amplitudes of rhythms compared between LD and DD were similar in pigment index, whereas a clear reduction was found for cone index, dopamine and melatonin.

Phagocytes in the axial complex of the sea urchin, Sphaerechinus granularis (Lam.). Fine structure and x-ray microanalysis.

In the axial complex of Sphaerechinus granularis intense phagocytotic activity is encountered. The phagocytes ingest morula cells and other phagocytes; a lysosomal digestion of the phagocytosed cells is suggested. A subdivision into early and late phagocytes is made according to their granular content. Most of the phagocytes possess intranuclear crystalloids that exhibit a filamentous or particulate substructure. Late stages of phagocytes filled with residual bodies and crystalloids leave the axial complex via the lacunar system to be removed through the rectum. X-ray microanalysis reveals a constant presence of iron and sulphur in the crystalloids. The residual bodies contain iron, sulphur, calcium and zinc in varying amounts. This study confirms that one function of the axial complex is excretion.

Ultrastructural, fluorescence microscopic and microfluorimetric study of the innervation of the axial complex in the sea urchin, Sphaerechinus granularis (lam.).

In juxtaposition with the contractile epithelia of the axial complex of the sea urchin, Sphaerechinus granularis, several types of nerve fibers with different vesicle populations were determined. Nerve terminals, filled with clear vesicles and dense core vesicles, form synaptoid neuromuscular junctions. Close to the somatocoelic epithelia of the axial and terminal sinus septa, numerous axon profiles form a nerve plexus. Among the epithelial cells covering the plexus, two types of nerve cells can be distinguished which presumably produce neurosecretory and aminergic granules, respectively. Monoamine fluorescence (formaldehyde-induced fluorescence, Falck-Hillarp technique) was analyzed microspectrofluorimetrically. The emission spectrum of the fluorophores occurring in the present material shows a maximum at 475 nm and is characteristic of catecholamines; the excitation maximum at 380 nm after formaldehyde treatment is typical of catecholamines at low pH only. Since the peak ratio (370:320 nm) does not change after HCl-vapor treatment, the fluorophores are likely to be indicative of dopamine.

Fine structure of the axial complex of Sphaerechinus granularis (Lam.) (Echinodermata: Echinoidea).

Three regions of the axial complex in Sphaerechinus granularis can be distinguished: 1) The axial organ which protrudes from one side of the axial sinus; the sinus septum which separates the sinus from the body cavity and encloses the stone canal; the pulsating vessel which runs along the inside of the axial organ. 2) The blindly-ending terminal sinus in which the pulsating vessel broadens out to the contractile terminal process. 3) The ampulla of the stone canal which connects the axocoel and water vascular system and which opens out through the madreporite. A single-layered, monociliated coelomic epithelium surrounds all regions of the axial complex. This epithelium contains smooth muscle cells at the contractile areas. Canaliculi, surrounded by basal lamina, are formed through infolding of epithelia; they end blindly in the fluid- and connective tissue-matrix of the inner structures. The lacunae of the dorso-ventral mesentery connect the periesophageal and the perianal haemal ring with the axial organ. The axial organ contains many coelomocytes rich in pigment and granules. These coelomocytes are separated into compartments by elastic fibres. Phagocytosis of whole cells and transformational stages of coelomocytes suggest storage and degradation functions. An excretory function via the water vascular system is also suggested.