[Prevalence and age-related changes of corneal astigmatism in patients before cataract surgery]. / Prävalenz und Altersabhängigkeit von kornealem Astigmatismus bei Patienten vor Kataraktchirurgie.

BACKGROUND: The aim of this study was to determine the extent and the distribution of corneal astigmatism in patients awaiting cataract surgery in a mid-European tertiary clinic centre and hence to establish the demand for methods reducing corneal astigmatism. PATIENTS AND METHODS: Keratometry measurements of cataract surgery candidates assigned to a university clinic between January 2013 and October 2014 were recorded and analysed retrospectively. RESULTS: A total of 6900 eyes of 3450 patients with a mean age of 72.5 ± 12.2 were analyzed. The corneal astigmatism was more than 0.5 dioptres (D) in 5193 eyes (75.3 %), >1.0 D in 2641 eyes (38.3 %), >1.5 D in 1304 eyes (18.9 %), >2.0 D in 644 eyes (9.3 %), >2.5 D in 363 eyes (5.3 %), >3.0 D in 236 eyes (3.4 %) and >3.5 D in 149 eyes (2.2 %). With increasing age a shift from with-the-rule astigmatism towards against-the-rule astigmatism was observed. CONCLUSION: Of the patients admitted for routine cataract surgery at our clinic, 2641 eyes (38.3 %) had an astigmatism greater than 1.0 D. Our data could be helpful in establishing a protocol for using toric intraocular lenses and to determine the costs.

Laser-assisted subepithelial keratomileusis with mitomycin C for myopic astigmatism ≥2.00 diopters using a Zeiss MEL 80 Excimer.

To examine the refractive and visual outcome of laser-assisted subepithelial keratomileusis (LASEK) with mitomycin C(MMC) in eyes with myopic astigmatism ≥2.00 diopters (D). This study comprised 82 eyes of 82 consecutive patients (37 male, 45 female; mean age at surgery 34.7 ± 9.0 years) with preoperative topographic astigmatism ≥2.00 D and mean preoperative spherical equivalent (SE) -4.50 ± 1.13 D. To assess whether the refractive results differed with the amount of corrected sphere, the data were separated by preoperative SE thereby defining two groups with SE < -5.00 D (-2.00 to -4.75 D) and ≥-5.00 D (-5.00 to -7.75 D). Mean manifest refraction spherical equivalent (MRSE) of -0.39 ± 0.52 D was obtained at the 6-months (5.4 ± 1.6 months) follow-up. The results were within ±1.00 D of the attempted correction in 89 % of patients. The mean postoperative corrected distant visual acuity was -0.02 ± 0.065 logMAR (range -0.10 to 0.15 logMAR). Sixty-seven (81.7 %) of all eyes did not change lines in safety. There was no statistically significant difference (P = 0.262) in safety between the SE groups. Mean efficacy was 0.89 ± 0.27. There was a statistically significant difference in efficacy (P = 0.024) between the preoperative SE groups. Larger ablation zones were associated with better visual outcome, confirmed by safety, efficacy and predictability. The data reported here demonstrated that LASEK using a Zeiss MEL 80 excimer laser with an additional application of MMC is a safe and efficient technique with predictable results for the correction of eyes with myopic astigmatism ≥2.00 D.

[Refractive predictability and stability of three-piece versus single-piece intraocular lenses in patients with high axial myopia]. / Refraktive Vorhersagbarkeit und Stabilität von 3-teiligen vs. 1-teiligen Intraokularlinsen bei hoher Achsenmyopie.

BACKGROUND: Based on previous data on single-piece and three-piece intraocular lenses (IOLs) there is no evidence for significant differences in decentration, tilt and refractive shift. The purpose of the current study was to compare single-piece and three-piece IOLs in patients with high axial myopia. MATERIAL AND METHODS: A total of 68 eyes of 50 patients with high axial myopia (axis length ≥ 28.00 mm) with and without cataract who underwent complication-free phacoemulsification and IOL implantation were retrospectively examined. To compare single-piece and three-piece IOLs, the patients were retrospectively grouped depending on IOL type: group 1 acrylic single-piece IOL (n = 37; ACR6D SE, Corneal, France) and group 2 acrylic three-piece IOL with fixed haptic frame (n = 31; AF-1 UY, Hoya, Japan). Patient files were analyzed regarding best spectacle-corrected visual acuity (BSCVA), refractive predictability and stability. RESULTS: In this study the mean BSCVA was determined as 0.22 ± 0.12 logMAR and 0.13 ± 0.11 logMAR 6 months postoperatively for the ACR6D SE group and the AF-1 UV group, respectively (p = 0.09). Refractive predictability was less accurate in the ACR6D SE (+ 1.75 ± 2.2 dpt) compared to the AF-1 UV (- 0.37 ± 1.1) treated eyes (p = 0.001). Refractive stability, defined as the difference in diopters between the first week and the sixth month after surgery, resulted in + 0.40 ± 1.7 dpt and -0.16 ± 1.2 dpt for the ACR6D SE and the AF-1 UV, respectively (p = 0.022). CONCLUSIONS: The three-piece AF-1 UV showed satisfactory refractive predictability and stability in patients with high axial myopia. The ACR6D SE has a high refractive unpredictability and should not be used in eyes with high axial myopia.

Borrelia burgdorferi in ticks and dogs in the province of Vojvodina, Serbia.

Lyme disease is a tick borne zoonotic infection, caused by Borrelia burgdorferi s.l. bacteria. For the transmission of the disease, the presence of ticks is a prerequisite. Lyme borreliosis mostly occurs in people and dogs, but it may occur in other animals. Ticks which carry B. burgdorferi s.l. in Serbia are of the Ixodes ricinus specis. In Serbia, Lyme disease was detected for the first time in the late '80-es. In dogs, clinical symptoms may occur even months after a tick bite, and include weakness, lymphadenopathy, fever, lameness, arthritis, etc. In our survey, we have observed tick and dog populations in the province of Vojvodina (northern part of Serbia). I. ricinus ticks were collected and examined for the presence of B. burgdorferi s.l. in several chosen locations. In addition, blood samples were collected from house dogs and pets from the same locations, and analyzed for the presence of antibodies specific for B. burgdorferi s.l. The results showed a mean infection of ticks of 22.12%, and a mean seroprevalence of Lyme disease in dogs of 25.81%. We conclude that in Vojvodina there is an actual risk of Lyme borreliosis for other animals and humans, because of the persistence of B. burgdorferi s.l. in both tick and dog populations.

[Visual function with blue light filter IOLs]. / Visuelle Funktion mit Blaulichtfilter-IOL.

BACKGROUND: Recently, intraocular lenses (IOLs) with a blue light filter have been introduced to protect the retina from age-related macular degeneration (AMD) after cataract extraction. A reduction of longitudinal chromatic aberration by filtering blue light may enhance patient's visual function. In this study we compared subjective and objective parameters of visual function following implantation of blue light filter (yellow) IOLs and IOLs of the same design without filter. PATIENTS AND METHODS: 21 patients (21 eyes) underwent implantation of an IOL with a blue light filter (AF-1 UY, Hoya, Japan), 22 patients (22 eyes) received an IOL without blue light filter (AF-1 UV, Hoya, Japan). Patients were examined three months postoperatively for uncorrected and best corrected spectacle visual acuity, mesopic and photopic contrast sensitivity, colour vision and subjective quality of vision by a standard questionnaire. RESULTS: Eyes with blue light filter IOLs did not show any significant difference in any parameter analysed when compared to eyes without the blue light filter IOL. Subjective quality of vision was considered to be high by all patients and no significant difference was observed between the two IOL groups. CONCLUSION: The visual function of patients with blue filter IOLs is not significantly different to those without blue light filter IOLs. Since blue light filter IOLs did not show any functional disadvantage, but potentially protect the macula from AMD, blue light filter IOLs may be considered as a reasonable alternative to traditional IOLs, especially in eyes with a high risk for the development of macular degeneration.

Functional characterization and expression of PBR in rat gastric mucosa: stimulation of chloride secretion by PBR ligands.

Previous studies have demonstrated that gastric mucosa contained high levels of the polypeptide diazepam binding inhibitor, the endogenous ligand of the peripheral-type benzodiazepine receptor (PBR). However, the expression and function of this receptor protein in these tissues have not been investigated. Immunohistochemistry identified an intense PBR immunoreactivity in the mucous and parietal cells of rat gastric fundus and in the mucous cells of antrum. Immunoelectron microscopy revealed the mitochondrial localization of PBR in these cells. Binding of isoquinoline PK 11195 and benzodiazepine Ro5-4864 to gastric membranes showed that fundus had more PBR-binding sites than antrum, displaying higher affinity for PK 11195 than Ro5-4864. In a Ussing chamber, PK 11195 and Ro5-4864 increased short-circuit current (I(sc)) in fundic and antral mucosa in a concentration-dependent manner in the presence of GABA(A) and central benzodiazepine receptor (CBR) blockers. This increase in I(sc) was abolished after external Cl(-) substitution and was sensitive to chloride channels or transporter inhibitors. PK 11195-induced chloride secretion was also 1) sensitive to verapamil and extracellular calcium depletion, 2) blocked by thapsigargin and intracellular calcium depletion, and 3) abolished by the mitochondrial pore transition complex inhibitor cyclosporine A. PK 11195 had no direct effect on H(+) secretion, indicating that it stimulates a component of Cl(-) secretion independent of acid secretion in fundic mucosa. These data demonstrate that mucous and parietal cells of the gastric mucosa express mitochondrial PBR functionally coupled to Ca(2+)-dependent Cl(-) secretion, possibly involved in the gastric mucosa protection.

Structural and functional study of reconstituted peripheral benzodiazepine receptor.

Recombinant mouse 18 kDa peripheral-type benzodiazepine receptor (PBR) protein was overexpressed in Escherichia coli and isolated using a His. Bind metal chelation resin. Recombinant PBR protein was purified with sodium dodecyl sulfate and reincorporated into liposomes using Bio-Beads SM2 as a detergent removing agent. Negative staining of the reconstituted PBR samples, examined by electron microscopy, showed the formation of proteoliposomes. Freeze-fracture of these proteoliposomes revealed the presence of transmembranous particles of an average size of 3.5 +/- 0.25 nm, consistent with the presence of a monomeric form of the recombinant PBR protein. The reconstituted protein exhibited the ability to bind both the PBR drug ligand isoquinoline carboxamide PK 11195 and cholesterol with nanomolar affinities. These data suggest that a PBR monomer is the minimal functional unit, binding drug ligands and cholesterol.

Structure, function and regulation of the mitochondrial peripheral-type benzodiazepine receptor.

Steroid biosynthesis begins with the transfer of cholesterol from intracellular stores into mitochondria. Through in vitro and in vivo studies using various steroidogenic cell models and with the help of pharmacological, biochemical, morphological and molecular approaches we demonstrated that the peripheral-type benzodiazepine receptor (PBR) is an 18 kDa mitochondrial protein that interacts with other proteins in the outer mitochondrial membrane to form a multimeric complex. PBR is required for the binding, uptake and release, upon ligand activation, of the substrate cholesterol. Thus, cholesterol becomes available to the inner mitochondrial membrane P450scc where steroid biosynthesis begins. The presence of mitochondrial PBR is also critical in maintaining outer mitochondrial membrane stability and in preventing apoptosis. Considering these functions of PBR and the fact that PBR is a ubiquitous protein, it is suggested that this drug receptor may serve as a target to control various mitochondrial and cell functions and to protect against experimentally or pathologically induced mitochondrial and cell toxicity.

The peroxisome proliferator perfluorodecanoic acid inhibits the peripheral-type benzodiazepine receptor (PBR) expression and hormone-stimulated mitochondrial cholesterol transport and steroid formation in Leydig cells.

The peroxisome proliferator perfluordecanoic acid (PFDA) has been shown to exert an antiandrogenic effect in vivo by acting directly on the interstitial Leydig cells of the testis. The objective of this study was to examine the in vitro effects of PFDA and identify its site of action in steroidogenesis using as model systems the mouse tumor MA-10 and isolated rat Leydig cells. PFDA inhibited in a time- and dose-dependent manner the hCG-stimulated Leydig cell steroidogenesis. This effect was localized at the level of cholesterol transport into the mitochondria. PFDA did not affect either the total cell protein synthesis or the mitochondrial integrity. Moreover, it did not induce any DNA damage. Morphological studies indicated that PFDA induced lipid accumulation in the cells, probably due to the fact that cholesterol mobilized by hCG did not enter the mitochondria to be used for steroidogenesis. In search of the target of PFDA, we examined its effect on key regulatory mechanisms of steroidogenesis. PFDA did not affect the hCG-induced steroidogenic acute regulatory protein (StAR) levels. However, it was found to inhibit the mitochondrial peripheral-type benzodiazepine receptor (PBR) ligand binding capacity, 18-kDa protein, and messenger RNA (mRNA) levels. Further studies indicated that PFDA did not affect PBR transcription, but it rather accelerated PBR mRNA decay. Taken together, these data suggest that PFDA inhibits the Leydig cell steroidogenesis by affecting PBR mRNA stability, thus inhibiting PBR expression, cholesterol transport into the mitochondria, and the subsequent steroid formation. Moreover, this action of PFDA on PBR mRNA stability indicates a new mechanism of action of peroxisome proliferators distinct from the classic transcription-mediated regulation of target genes.

In vitro studies on the role of the peripheral-type benzodiazepine receptor in steroidogenesis.

In vitro studies using isolated cells, mitochondria and submitochondrial fractions demonstrated that in steroid synthesizing cells, the peripheral-type benzodiazepine receptor (PBR) is an outer mitochondrial membrane protein, preferentially located in the outer/inner membrane contact sites, involved in the regulation of cholesterol transport from the outer to the inner mitochondrial membrane, the rate-determining step in steroid biosynthesis. Mitochondrial PBR ligand binding characteristics and topography are sensitive to hormone treatment suggesting a role of PBR in the regulation of hormone-mediated steroidogenesis. Targeted disruption of the PBR gene in Leydig cells in vitro resulted in the arrest of cholesterol transport into mitochondria and steroid formation; transfection of the mutant cells with a PBR cDNA rescued steroidogenesis demonstrating an obligatory role for PBR in cholesterol transport. Molecular modeling of PBR suggested that it might function as a channel for cholesterol. This hypothesis was tested in a bacterial system devoid of PBR and cholesterol. Cholesterol uptake and transport by these cells was induced upon PBR expression. Amino acid deletion followed by site-directed mutagenesis studies and expression of mutant PBRs demonstrated the presence in the cytoplasmic carboxy-terminus of the receptor of a cholesterol recognition/interaction amino acid consensus sequence. This amino acid sequence may help for recruiting the cholesterol coming from intracellular sites to the mitochondria.

Peripheral-type benzodiazepine receptor (PBR) in human breast cancer: correlation of breast cancer cell aggressive phenotype with PBR expression, nuclear localization, and PBR-mediated cell proliferation and nuclear transport of cholesterol.

Aberrant cell proliferation and increased invasive and metastatic behavior are hallmarks of the advancement of breast cancer. Numerous studies implicate a role for cholesterol in the mechanisms underlying cell proliferation and cancer progression. The peripheral-type benzodiazepine receptor (PBR) is an Mr 18,000 protein primarily localized to the mitochondria. PBR mediates cholesterol transport across the mitochondrial membranes in steroidogenic cells. A role for PBR in the regulation of tumor cell proliferation has also been shown. In this study, we examined the expression, characteristics, localization, and function of PBR in a battery of human breast cancer cell lines differing in their invasive and chemotactic potential as well as in several human tissue biopsies. Expression of PBR ligand binding and mRNA was dramatically increased in the highly aggressive cell lines, such as MDA-231, relative to nonaggressive cell lines, such as MCF-7. PBR was also found to be expressed at high levels in aggressive metastatic human breast tumor biopsies compared with normal breast tissues. Subcellular localization with both antibodies and a fluorescent PBR drug ligand revealed that PBR from the MDA-231 cell line as well as from aggressive metastatic human breast tumor biopsies localized primarily in and around the nucleus. This localization is in direct contrast to the largely cytoplasmic localization seen in MCF-7 cells, normal breast tissue, and to the typical mitochondrial localization seen in mouse tumor Leydig cells. Pharmacological characterization of the receptor and partial nucleotide sequencing of PBR cDNA revealed that the MDA-231 PBR is similar, although not identical, to previously described PBR. Addition of high affinity PBR drug ligands to MDA-231 cells increased the incorporation of bromodeoxyuridine into the cells in a dose-dependent manner, suggesting a role for PBR in the regulation of MDA-231 cell proliferation. Cholesterol uptake into isolated MDA-231 nuclei was found to be 30% greater than into MCF-7 nuclei. High-affinity PBR drug ligands regulated the levels of cholesterol present in MDA-231 nuclei but not in MCF-7. In addition, the PBR-dependent MDA-231 cell proliferation was found to highly correlate (r = -0.99) with the PBR-mediated changes in nuclear membrane cholesterol levels. In conclusion, these data suggest that PBR expression, nuclear localization, and PBR-mediated cholesterol transport into the nucleus are involved in human breast cancer cell proliferation and aggressive phenotype expression, thus participating in the advancement of the disease.

Effect of unilateral and bilateral lesions of caudate-putamen on immune response in the rat.

In the present study we investigated the effect of selectivity destroyed dopaminergic neurons of the caudate-putamen (CP) on immune reactivity in the rat. Unilateral and bilateral lesioning of CP was performed by one direct stereotaxic injection of 6-hydroxydopamine solution. Sham-lesioned and intact rats served as controls. Two weeks after the operation, the animals were immunized with sheep red blood cells or bovine serum albumin for determination of plaque forming cell-response and Arthus and delayed hypersensitivity skin reactions, respectively. Unilateral and bilateral lesions of CP considerably suppressed PFC-response and Arthus and delayed the hypersensitivity reactions in comparison to control rats, while no differences were observed between unilaterally and bilaterally lesioned animals.

Acute action of choriogonadotropin on Leydig tumor cells: qualitative and quantitative transformation of lipid moieties.

BACKGROUND: Testicular Leydig cells use either exogenous or de novo synthesized cholesterol as the substrate for the production of testosterone with hormone stimulation. Although the long-term effect of trophic hormones on Leydig cell cholesterol uptake, storage, and deesterification has been well documented, the early effects of the human choriogonadotropin (hCG) on cell cholesterol/lipid distribution are not yet known. METHODS: Sections of cells treated with hCG for 15 sec to 30 min were examined by electron microscopy (EM) for the surface density of lipid moieties in the cytoplasm. In addition, the time-dependent distribution of lipids within the cytoplasmic inclusions and the ultimate destination of this substrate were evaluated by EM. The results were analyzed with standard morphometric methods. RESULTS AND CONCLUSION: The surface density of cytoplasmic lipid pools increased significantly within the 15 sec following the exposure of cells to hCG, and it tapered off to the control level in the subsequent 30 min. Such a fluctuation in the amount of cytoplasmic lipids may be due to (1) the quantity of released substrate from the reticular compartment or (2) the rate of its transport across the outer mitochondrial membrane to the inner mitochondrial cytochrome P450 side-chain cleavage, where steroidogenesis begins with the conversion of cholesterol to pregnenolone. These two processes were not quantitatively coordinated in the stimulated cell during the initial 30 min, resulting in a surplus of cytoplasmic lipid pools. To compensate for such uneven metabolic balance, the cell apparently disposed of the excess substrate by a mechanism of molecular regrouping from a micellar configuration to a bilayer structure followed by exocytosis.

Regulation of rat testis gonocyte proliferation by platelet-derived growth factor and estradiol: identification of signaling mechanisms involved.

To determine what factors regulate gonocyte proliferation in newborn rats, we first examined the expression of several signal transduction molecules by immunocytochemistry in 3-day-old rat testis sections. We found that gonocytes specifically expressed the iota and zeta isoforms of protein kinase (PK) C (PKC) and the phosphatidylinositol 3-kinase (PI3-K). Because both the zeta PKC and PI 3-K have been shown to play a role in platelet-derived growth factor (PDGF)-induced cell proliferation, we examined the effects of PDGF on gonocytes. For this, we developed a method to obtain highly purified and viable gonocytes in culture. After enzymatic digestion, differential adhesion, and two successive gradient fractionations, the gonocyte suspension obtained was over 90% pure, as assessed by light microscopy. The viability of cultured gonocytes exceeded 90% after 48 h in the presence of 2.5% FBS used as a survival factor. Immunodetection studies showed that isolated gonocytes expressed zeta PKC, PI 3-K, and the PDGF receptor. Treatment with 10 ng/ml PDGF induced a 4-fold increase of bromodeoxyuridine incorporation into gonocytes (from 5% proliferative gonocytes under basal conditions to 20% in the presence of PDGF). Because neonatal Sertoli cells secrete high levels of the growth promoting steroid, 17 beta-estradiol, we also tested its effect and found that it induced gonocyte proliferation at a level comparable with that of PDGF and that this effect was blocked by the estrogen receptor antagonist, ICI 164384. The combination of PDGF and estradiol, however, was not additive, suggesting that their effects were mediated by common molecular target(s). These results demonstrate that PDGF and estradiol activate gonocyte proliferation in vitro, suggesting that they may act as the physiological regulators of gonocyte development in vivo.

Atomic force microscope imaging of DNA and DNA repair proteins: applications in radiobiological research.

By using the atomic force microscope (AFM), three-dimensional structures of biological specimens may be imaged at nanometer resolution. Furthermore, samples can be imaged in air or in fluid environments. The tapping mode of AFM operation for imaging has offered a significant advance in visualizing soft biological structures, such as DNA, proteins, and membranes. Here, we review the principles underlying the application of this instrument to radiation biological investigations. We focus on examples of proteins involved in the processes of repair of damaged DNA, including poly(ADP-ribose) polymerase, Ku protein, and DNA protein kinase. Novel observations on the character of DNA damage and repair have been addressed by direct visualization of DNA and protein-DNA interactions, such as the observation that the Ku protein is capable of physically joining DNA fragments in vitro. The AFM offers a powerful tool for investigating biologically important molecular interactions that are relevant to DNA damage and repair processes.

Peripheral benzodiazepine receptor in cholesterol transport and steroidogenesis.

Steroidogenesis begins with the metabolism of cholesterol to pregnenolone by the inner mitochondrial membrane cytochrome P450 side-chain cleavage (P450scc) enzyme. The rate of steroid formation, however, depends on the rate of cholesterol transport from intracellular stores to the inner mitochondrial membrane and loading of P450scc with cholesterol. In previous in vitro studies, we demonstrated that a key element in the regulation of cholesterol transport is the mitochondrial peripheral-type benzodiazepine receptor (PBR). We also showed that the polypeptide diazepam binding inhibitor (DBI), an endogenous PBR ligand, stimulates cholesterol transport and promotes loading of cholesterol to P450scc in vitro, and that its presence is vital for hCG-induced steroidogenesis by Leydig cells. Based on these data and the observations that i) the mitochondrial PBR binding and topography are regulated by hormones; ii) the 18-kDa PBR protein is functionally coupled to the mitochondrial contact site voltage-dependent anion channel protein; iii) the 18-kDa PBR protein is a channel for cholesterol, as shown by molecular modeling and in vitro reconstitution studies; iv) targeted disruption of the PBR gene in steroidogenic cells dramatically reduces the ability of the cells to transport cholesterol in the mitochondria and produce steroids; v) endocrine disruptors, with known anisteroidogenic effect, inhibit PBR ligand binding; and vi) in vivo reduction of adrenal PBR expression results in reduced circulating glucocorticoid levels, we conclude that PBR is an indispensable element of the steroidogenic machinery.

Targeted disruption of the peripheral-type benzodiazepine receptor gene inhibits steroidogenesis in the R2C Leydig tumor cell line.

To evaluate the role of the mitochondrial peripheral-type benzodiazepine receptor (PBR) in steroidogenesis, we developed a molecular approach based on the disruption of the PBR gene, by homologous recombination, in the constitutive steroid producing R2C rat Leydig tumor cell line. Inactivation of one allele of the PBR gene resulted in the suppression of PBR mRNA and ligand binding expression. Immunoblot and electron microscopic immunogold labeling analyses confirmed the absence of the 18-kDa PBR protein in the selected clone. Although mitochondria from the PBR-negative cells contained high levels of the constitutively expressed 30-kDa steroidogenic activity regulator protein, these cells produced minimal amounts of steroids compared with normal cells (5%). Moreover, mitochondria from PBR-negative cells failed to produce pregnenolone when supplied with exogenous cholesterol. Addition of the hydrosoluble cholesterol derivative, 22R-hydroxycholesterol, increased steroid production by the PBR-negative R2C cells, indicating that the cholesterol transport mechanism was impaired. Stable transfection of the PBR-negative R2C Leydig cells with a vector containing the PBR cDNA resulted in the recovery of the steroidogenic function of the cells. These data demonstrate that PBR is an indispensable element of the steroidogenic machinery, where it mediates the delivery of the substrate cholesterol to the inner mitochondrial side chain cleavage cytochrome P-450.

Anatomical variant of the lateral pectoral nerve innervating the anterior portion of the deltoid muscle: a case report.

BACKGROUND: The deltoid muscle is innervated by the axillary nerve. There is no collateral nerve supply described for this muscle. Palsy of the axillary nerve is common in shoulder trauma due to its close relationship to the surgical neck of humerus. METHODS: A dissection of the pectoral and axillary regions of two female cadavers was performed bilaterally for a detailed analysis of the innervation of the deltoid muscle. RESULTS: A branch of the lateral pectoral nerve provided supplemental innervation to the anterior portion of the deltoid muscle bilaterally in both cadavers. CONCLUSION: A branch of the lateral pectoral nerve could provide collateral nerve supply to the deltoid muscle. The frequency of this anatomical variation requires further exploration.

Acute action of choriogonadotropin on Leydig tumor cells: changes in the topography of the mitochondrial peripheral-type benzodiazepine receptor.

We examined the topography of the MA-10 Leydig tumor cell mitochondrial peripheral-type benzodiazepine receptor (PBR). In previous studies, the 18 kDa PBR was found to be functionally associated with the voltage-dependent anion channel, located in the junctions between outer and inner membranes. Transmission electron (TEM) and atomic force microscopy (AFM) of immunogold labeled PBR on Leydig cell mitochondrial preparations showed that the 18 kDa PBR protein is organized in clusters of 4-6 molecules. Addition of hCG to Leydig cells induces a rapid, within 30 sec, increase in PBR ligand binding and morphological changes, namely redistribution of PBR molecules in large clusters (>7 particles). These hCG-induced changes were inhibited by a cAMP-dependent protein kinase inhibitor and by the benzodiazepine flunitrazepam. AFM further demonstrated the rapid reorganization of the mitochondrial membrane, where the formation of contacts between the outer and the inner mitochondrial membrane may facilitate cholesterol transfer.

A morphometric and functional study of the toxicity of atmospheric ammonia in the extrathoracic airways in pigs.

The effects of atmospheric ammonia (NH3) on the nasal and tracheal mucosa of pigs were investigated by morphometric and functional methods. Pigs were exposed to four concentrations of NH3 [5 (control), 25, 50 and 100 ppm] for 6 days in a specially designed air-pollutant exposure chamber. Samples were taken from the turbinates and the trachea, and the respiratory mucosa was examined by light and scanning electron microscopy. Dose-response curves to carbachol and isoproterenol were constructed using isolated strips of tracheal smooth muscle, with or without epithelium. In pigs exposed to ammonia, considerable mucosal injuries were observed in the turbinates but not in the trachea. The number of neutrophils in the epithelial layer and in the lamina propria, and epithelial hyperplasia were closely and significantly correlated with the concentrations of ammonia (r = 0.894, p < 0.001; r = 0.727, P < 0.001; and r = 0.818, p < 0.001, respectively). Except for the lamina propria, all these changes were significant (p < 0.05) at ammonia concentrations as low as 25 ppm. The percentage of the surface of the turbinate mucosa that was ciliated tended to decrease with increasing ammonia concentration (r = 0.439, p < 0.082). Ammonia induced smooth-muscle hyperresponsiveness to carbachol with a close linear correlation between individual values of the carbachol-induced maximal effect and the NH3 concentrations (r = 0.526, p < 0.003). While mechanical destruction of the epithelium induced an increase in Emax in the control group, no difference was observed between the intact and denuded strips from animals exposed to ammonia. The response to isoproterenol was not influenced by ammonia. It was concluded that quantitative histological analysis of the inflammatory infiltration and epithelial hyperplasia in the turbinates is a useful tool for quantifying the effects of atmospheric pollutants in pigs; a 6-day exposure to ammonia induces nasal irritation and functional disturbances of the tracheal smooth-muscle contractions at concentrations as low as 25 ppm.