Biotransformations of monoterpenes by photoautotrophic micro-organisms.

Monoterpenes are widely used in food technology, cosmetic and pharmaceutical industries and as compounds of agricultural importance. It is known that compounds comprising this class can be transformed by a variety of organisms, namely by: bacteria, fungi, yeasts, plants or isolated enzymes. Biotransformations, as one of the most important tools of green chemistry, allow obtaining new products using whole cells of micro-organisms or isolated enzymes in mild reaction conditions. Therefore, biotransformations of monoterpenes, by different type of reaction such as: epoxidation, oxidation and stereoselective hydroxylation, resulted in the production of so desired, enantiomerically defined compounds that can be advised as natural seem to be interesting. Bearing in mind that such processes are carried out also by easy to maintain, photoautotrophic micro-organisms cultivated at large scale, this paper is focused on biotransformations of acyclic, monocyclic and bicyclic monoterpenes by freshwater or haliphylic cyanobacteria and microalgae on the way of mainly stereoselective hydroxylation. Moreover, aspects of potential industrial application of obtained products in medicine, perfume, cosmetics and food industry are discussed.

[Delayed DMCA-flap in a case of infection in the finger]. / Zweizeitige DMCA-Lappenplastik bei infektbedingtem palmarem fingerweichteildefekt.

INTRODUCTION: After its first description 1990 by Maruyama, the DMCA flap has been used for several indications. In 1999 Pelissier published his "extended DMCA flap" with a wider arc of rotation. Compared to the most frequent indications for the DMCA flap, palmar digital soft tissue defects after infection are rare. CASE REPORT: A 35-year-old male stockman presented with a severe phlegmonous infection of the middle finger. Repeated debridements led to a soft tissue defect on the palmar side of the middle finger. After vain initial attempts the patient quit smoking and the DMCA II and III could be detected by ultrasonic Doppler probe. An extended DMCA II flap was performed to cover the soft tissue defect. Due to acute intraoperative ischaemia of the flap after elevation and rotation, the flap was repositioned to the donor site. After preconditioning for ten days, the transposition of the flap could be performed without any further problems. There were no postoperative complications. The length and the form of the finger could be preserved. CONCLUSION: Even in the case of palmar soft-tissue defects due to infections, the expanded DMCA flap may be a valuable option for coverage. It may be possible to localise the dorsal metacarpal arteries by ultrasonic Doppler probe in a smoking patient after a period time of nicotine abstinence, if initial attempts at detection fail. If the perfusion of the rotated extended DMCA flap appears to be compromised, we recommend the repositioning of the flap. Its transposition may be safely performed after a preconditioning period.

Ligands for expression cloning and isolation of GABA(B) receptors.

Outlined is the rationale behind the syntheses of radioligands [125I]CGP64213 and [125I]CGP71872, which led to the identification of cloned GABA(B) receptors 1a and 1b 17 years after the first pharmacological characterisation of native GABA(B) receptors by Bowery et al. [Nature 283 (1980) 92-94]. More recently it was shown that the N-terminal extracellular domains of GABA(B) receptors 1a and 1b contain the binding sites for agonists and antagonists [B. Malitschek et al., Mol. Pharmacol. 56 (1999) 448-454]. In order to isolate the extracellular domain(s) of GABA(B) receptors 1a (or 1b) and to purify and crystallise these proteins a third ligand [125I]CGP84963 was designed, which combines, in one molecule, a GABA(B) receptor binding part, an azidosalicylic acid as photoaffinity moiety and 2-iminobiotin, which binds to avidin in a reversible, pH-dependent fashion [W. Froestl et al., Neuropharmacology 38 (1999) 1641-1646].

Squamous cell carcinoma developing in an intracranial prepontine epidermoid cyst.

Intracranial epidermoid cysts represent around 0,2 to 1 % of all intracranial tumours. Rare malignant transformation of these benign lesions may occur. A 66-year-old man presented with a state of confusion. MRI demonstrated a heterogeneous signal in front of the pons and ventricular dilatation. Cerebrospinal fluid examinations disclosed inflammatory cells. The patient died six months after his first admission to hospital. At autopsy, a firm greyish tumour (3 cm-long and 1 cm-thick) was present in front of the brain stem encasing the basilar artery. Microscopic examination revealed a well-differentiated epidermoid carcinoma arising from a cystic lesion whose wall was lined by a squamous epithelium with a benign appearance. The walls of all the ventricles were lined by carcinomatous cells. There was no leptomeningeal metastasis. Twenty three other cases of such squamous cell carcinoma have been reported and most of them had died within a few months.

Ligands for the isolation of GABA(B) receptors [corrected] .

Since the discovery that the most abundant inhibitory neurotransmitter in the mammalian brain, GABA (gamma-aminobutyric acid), interacts not only with ionotropic GABA(A) receptors, but also with metabotropic GABA(B) receptors (Bowery et al., 1980) much work has been devoted to the elucidation of the structure of GABA(B) receptors by either affinity chromatography purification or by expression cloning. In 1997 Kaupmann et al. succeeded in cloning two splice variants designated GABA(B) R1a (960 amino acids) and GABA(B) R1b (844 amino acids). Although the amino acid sequences are now known, precise information on the three-dimensional environment of the GABA(B) R1 binding site is still lacking. Recent experiments demonstrated that the amino acids of the seven transmembrane helices are not essential for ligand binding as a soluble GABA(B) receptor fragment is still able to bind antagonists (Malitschek et al., 1999). For the isolation and purification of the soluble N-terminal extracellular domain (NTED) of GABA(B) receptors potent ligands for affinity chromatography were synthesised with the aim of obtaining a crystalline receptor fragment-ligand complex for X-ray structure determination. The most promising ligand [125I]CGP84963 (K(D) = 2 nM) combines, in one molecule, a GABA(B) receptor binding part, an azidosalicylic acid as a photoaffinity moiety separated by a spacer consisting of three GABA molecules from 2-iminobiotin, which binds to avidin in a reversible, pH-dependent fashion.

Phosphinic acid analogues of GABA. 1. New potent and selective GABAB agonists.

The antispastic agent and muscle relaxant baclofen 1 is a potent and selective agonist for bicuculline-insensitive GABAB receptors. For many years efforts to obtain superior GABAB agonists were unsuccessful. We describe the syntheses and biological properties of two new series of GABAB agonists, the best compounds of which are more potent than baclofen in vitro and in vivo. They were obtained by replacing the carboxylic acid group of GABA or baclofen derivatives with either the phosphinic acid or the methylphosphinic acid residue. Surprisingly, ethyl- and higher alkylphosphinic acid derivatives of GABA yielded novel GABAB antagonists, which are described in part 2 of this series. Structure-activity relationships of the novel GABAB agonists are discussed with respect to their affinities to GABAB receptors as well as to their effects in many functional tests in vitro and in vivo providing new muscle relaxant drugs with significantly improved side effect profiles.

Phosphinic acid analogues of GABA. 2. Selective, orally active GABAB antagonists.

In 1987, 25 years after the synthesis of the potent and selective GABAB agonist baclofen (1), Kerr et al. described the first GABAB antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABAB antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABAB antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABAB receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABAB antagonists interacted also with postsynaptic GABAB receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABAB antagonists showed also protective effects in various animal models of absence epilepsy.

Radiographic characteristics of central ossifying fibroma.

Sixty-four instances of histologically documented ossifying and/or cementifying fibromas were evaluated. Adequate radiographs were available in 43 of the cases. Most of these benign fibro-osseous neoplasms occurred in women, with a predilection for the third and fourth decades. Six distinct radiographic patterns could be identified: (1) radiolucent, superimposed over teeth or residing in edentulous regions (28%); (2) radiolucent with opaque foci, lying in edentulous areas or superimposed over teeth (42%); (3) radiolucent, interposed between contiguous teeth (5%); (4) radiolucent with opaque foci, interposed between contiguous teeth (9%); (5) multilocular expansile (7%); and (6) aggressively expansile with opacification (9%). All lesions exhibited well-defined margins. Root resorption was a feature in 11% of the sample, and root divergence occurred in 17% of the cases.

Focal sclerosing osteomyelitis/focal periapical osteopetrosis: radiographic patterns.

Forty-one histologically documented instances of focal sclerosing osteomyelitis and focal periapical osteopetrosis have been evaluated for radiomorphologic characteristics. These reactive lesions exhibit five distinct patterns that include periapical focal opacifications, target lesions, radiolucencies, multiconfluent configurations, and opacifications with concomitant root resorption. While an irritational origin can usually be detected in chronic sclerosing osteomyelitis, the cause of focal periapical osteopetrosis remains enigmatic.

Radiographic characteristics of cystogenic ameloblastoma.

Radiographic patterns encountered in mandibular cystogenic ameloblastoma, a variant encountered among teen-agers and young adults, are described and correlated with age and recurrence after surgery. More than 75% of the cases are located in the posterior mandibular ramus area, and 50% are associated with an impacted third molar. The predominant radiographic patterns include unilocular and scalloped or macromultilocular pericoronal , interradicular , or periapical expansile radiolucencies.