Document KR7KgXKevY5oeaVmgoJyLpQ

|M.wi did (<n basic r*y can lions elrt on ca f/:/' 7 F.xpcnentia (1919), Rirkhluser Vcrlag. Bawl (Schweiz) the mode of action of substances causing neuronal depolar ization For instance, ouabaine, an inhibitor of Na*-K * ATPaae1" in contrast to MBP, did not cause any shape change in platelets. This indicates that the MBP-induced shape change cannot be due to inhibition of Na+-K*> A'TPase, and that the depolarizing effects of ouabaine* and of MBP in neuronal cells may well have different natures. Platelets might also be used to screen for substances ah^ to antagonize the effects of MBP on membranes, which would be of potential interest for demyebnating diseases e g. multiple srlcrosis. In these disorders proteins seem to be liberated fiom the myelin sheaths, whose content of MBP, but not or histones, is quite high'* Indeed, increased amounts of MRP-like material have been found in the cerebrospinal fluid of patients with demyebnating disordcrsw 33. If these proteins were to act on neurons! mem* branes this might cause neurological manifestations e.g. during episodes of acute exacerbation of the disease. Final ly, it may be of interest to investigate whether there is a difference between platelets of patients with demyebnating disorders and those from healthy controls in their reaction to MBP. 1 Acknowledgment. We thank Miss 8. Gieux and Miss M. Handmhin for skilful technical assistance. 2 M Graf and A. Fleischer, Br. J Pharmac.. in press (1979). 3 M. Graf. A. I.aubscher. J. G. Richards and A. Pletscher, J. clio. Lab Invest., in press (1979). iiwi 4 F. Michal and G Bom. Naiutc 2St, 220 (19/1) 5 G E. Dciblcr, R E. Martenson and M.W Kixy Tin, Bio- chem. 2, 139(1972). P 6 f,R Dunkley .nd H I. Cmwp,. R . ,1Lh Mc,h.i, Nturochcii.iilrv, vol.\ p 215 Ed. N. Mai. . and R. Kndn.al,i Plenum Press. New York 1974 * 7 j/lJUw") P J Br*erd'n* *nd D L C'Tat'V Stain Ir.hm.l, 8 H.J. Weiss, New Engl. J. Med 293. 531 (1975) 9 f)979)GlhW'Ier ***** 1 Hune**er' N6'"'"'''-'* ' 11. 317 10 CG. Honegger, B.H. Gsbwiter and H. tler. NturnKi Lett * 303(1977). 1 11 K.A. Grttlubf Wtromb Diaih. haemorrh. 21. 430(19*9) 12 C S P. Jankins, M.A. f. kham, R L. Kinlough-IUthhonc and J.F. Mustard, Blaod 37. 395 (1971). 13 J.G. White, Am. J Path. A* 447 (1972) 14 H".J` Ryser, Science 159. 390(19*8). 15 R.T adley and C. Trachtenberg Hrain Res / W. I (I97S) 16 Y.l keiumi snd A. Kuramotn, ; fombo*. Hacmosus ><> ll (19' ` 17 P. Msssini, l C. Metcalf. U. Nafand E. K Ulschcr Haenio-.- tasu J, 8 (197-1). 18 J.L. Moake, K. Ahmed. N R. Bachur and l> F.. Gudrcumf. Biochim. biophys. Acta 211. 337 (1970). 19 P.E. Braun and S.W, BrostofT. m Myelin, p201 Ed P. Morell. Plenum Press, New York 1977. 20 S.R. Cohen, R M. Herodoa and G.M. McKhann, New ting) J. Med 205. 1455(1976). 21 S.R. Cohen and H.S. Guutein, Science 199, 301 (I97> 22 J.H. Carson, E. Barbarese, P.E. Braun and T A. McPherson. Proc. nal. Acad. Sd. USA 75, 1976 (1978) \%T Effect of the polychlorinated biphenyl preparation, Aroclor 1242, on the quantity of neurosecretory material in the medulla terminal!* X-organ of the fiddler crab, Ucapngiiator1 R. Nagabhushanam, S.W. Fingerman and M. Fingerman3 Department of '/.oology, Marathwoda University. Aurangabad (India) and Department of Biology, Tulane Universal, New Orleans (Utuisiana 70118, USA). 20 October 1978 Summary. Exposure of the fiddler crab. Uca pugilafor, to the PCB preparation, Aroclor 1242, produces an increase in the quantity of neurosecretory material in the medulla (erminalis X-organ. This Aroclor apparently inhibits release, but not synthesis, of one or more neurohormones. Polychlorinated biphenyls (PCBs) arc extremely persistent, globally distributed pollutants3. Many animals, including the fiddler crab. Uca pugflator, the species used in this investif;i)ion, have been found to accumulate PCBs in their tissues4 Exposure of this crab to the PCB preparation, Aroclor 1242, results in decreased dispersion of the pigment in its mclanophore*1. Those crabs exposed to Aroclor 1242 had up to 4 times more melanin-dispersing hormone (MI>H), a ncurohormonc. in their eyestalks than did con trol crabs. The PCB preparation appeared to inhibit MDH release but nol its synthesis. In the eyestalk of the fiddler crab, MDH is released from (he sinus glands. These glands are neurohemal organs. Most, if not all, of the neurosecre tory axons that enter a sinus gland originate in the medulla (erminalis X-organ of each eyestalk. In a recent study of (he eyestalk of (lie crayfish, Orconectes virtlis, the investigators could find no evidence that neurosecretory axons came from any other area than the medulla terminaiis X-organ6, The object of this investigation was to determine whether cytologies) evidence of an effect of Aroclor 1242 on the neuroendocrine system of (he fiddler crab could be ob tained. Materials and methods. Mattie female specimens of Uca pugilator. having a carapace width of 1.5-1.6 cm, from the area of Panacea, Florida, were used. At noon, crabs were sci-cted from the stock supply and placed in white enam eled pans (18 cm diameicr) containing artificial sea waicr (Instant Ocean, Aquarium Systems) . lone, and placed under a const.nt illumination of 2IX lux at 24 X. 24 h later those crabs whose melanophores were at HoghcnSlome stage 3 were selected for further use7. According (o the Hogben-Slome scheme stage 3 represents an interme diate degree of pigment dispersion with stage I represent ing maximal concentration of the pigment and stage 5 maxima) dispersion. The selected crabs were then divided into 2 groups and placed into white enameled pans which contained either 8 ppm Aroclor 1242 (Monsanto Lot Num ber G26elC) in a solution of 0.1% acetone in artificial sea water or only 0.1% acetone in artificial sea water. The Aroclor had first been dissolved in acetone which explains (he presence of acetone in both the experimental and control containers. The volume of liquid in each pan was 400 ml. The 2 groups of crabs were again exposed to the constant illumination of 2IX lux at 24 *C for 24 h after which their melanophore stages were again determined and their eyestalks were removed. The internal tissues of both eyestalks from 5 experimental and 5 control cribs were then dissected out, fixed in Bouin's solution, embedded in paraffin, cut into longitudinal serial "sections 8 pm thick, and stained with Gomori's chrome-alum hematoxylin and MONS 085898 IOM Experienii* 35 (l979)PBirlbluser Verlag. Basel (Schweiz) Neurosecretory activity in the medulla lerminslu X-organ PCS-treated Crab aumber I 2 3 4 5 Staining index 2 3 2 3 3 Control 1 2 3 4 5 Avenge 2.6* I 1 2 2 * Significantly greater than control (p < 0.03). Average 1.4 phloxin*. The secretory activity of the neurosecretory cel! bodies in the medulla trrminalis X-organ of the sectioned eycslulks was then evaluated by using the following index r .unbent to stage the cells: 0, neurosecretory granules absent; I. very few granules; 2, intermediate between ' and 3; 3, a large number of granules. This system is essentially that of Matsumoto, but he numbered his stages 0, 1,3, and 5*. A cell whose cytoplasm is crowded with neurosecretory granules presumably contains more neurohonnonc than does a cell with .ew or no granules. Statistical evaluation of the data was performed uaing the Student's i-test. Results and discussion. When the eyestalks were removed, the mean melanophore stage of the crabs that had been in the acetone-sea water for 24 b was 3.4 whereas that of the crabs in the PCB preparation was 1.7. This difference (3.4 versus 1.7) and the decrease from the initial melanophore stage (1.7 versus 3.0) were not only statistically significant (p<0.0l for both) but were also consistent with the pre* vious observation that Aroclor 1242 prevents the pigment in the melanophoivs from remaining as dispersed as in con trol crabs1. The slightly increased level of melanin disper sion, up fror* the original 3.0 to 3.4, in the control crabs was presumably due in large measure to the continuous expo sure to the bright illumination (2100 lux) in contrast to the 422 lux the cr>bs had been exposed to in the stock tank prior to the siurt of the experiment. Bright illumination induces melanin dispersion in the fiddler crab10. Examination of the eyestalk sections revealed that the quantity of neurosecretory material in the neurosecretory cell bodies in the medulla terminalis X-organs of the crabs exposed to the PCB preparation was significantly greater than in the control crabs (table). This observation is consis tent with the previously obtained data which showed that eyestalks of crabs exposed to Aroclor 1242 contained more MDH than did eyestalks of control crabs5. Ot cou- .e. all of the neurosecretory granules stained were not MDH-con- taining alone. The eyestalk secretes several different neuro* hormones". Additional experiments are being periormcd to determine what eyestalk neurohoimones in addition to MDH are also affected by PCBs. 1 This investigation wn supported by grant PCM75-03029 A01 from the National Science Foundation. 2 Reprint requests should be addressed to M F 3 R.W. Risebrough, P. Rieche. D.P. Pcakall, S.G. Kerman and M.N.Kirven, Nature220, 1098(1968). 4 D.R. Nimmo, P.D. Wilson, R.R. Blackman and A.J Wibon. Jr, Nature231. 50(1971). 5 S.W. Fingerman and M. Fingerman. Mar. Biol. 50. 37 (1978). 6 R.D. Andrew, 1. Orchard and A.S.M. Salcuddin, Ceil Tiss. Rea./KJ. 235(1978). 7 L. Hogben and D. Slorne, Proc. r. Soc. Lond. I08B. 10(19)1). 8 G. Gomori, Am. J. Path. 57, 395 (1941). 9 K. Matsumoto, Gen. comp. Endocr. 2, 4 (1962). 10 F A. Brown, Jr, and M.l. Sandeen, Physiol. Zool. 21. 361 (1948). 11 L.H. Kleinholz, Am. Zool. 16. 151(1976). MGNS 065899 Glomerular filtration rate and kidney Mood flow in alloxan and streptozotocln diabetic rats J.M.Foy and A. K.M. Salih School ofStudies in Pharmacology, University ofBradford, Bradford West, Yorkshire BD71DP (England). 3 November 1278 Summary C 'omerular (V(ration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetioratt at different times after the administration of diabeiogen. A high GFR was found together with increased kidney weight and reduced blood flow. * .. The role of diabetic nephropathy as a cause of death in late increase in RPF, a decrease in RPF and hence a higher diabetes mellitus underlines the importance of studying filtration pressure or to an increase in the permeability changes in renal structure and function early in the disease. of the glomeruli. Increased kidney size was also reported to A measurable thickening of the basement membrane and be behind this abnormality* *. mesangial region has been clearly shown in recent studies All the previously mentioned studies were carried out on using the electron microscope. It lakes place long before human beings where ethical considerations limit the nature (he advent of any clinval evidence of nephropathy1'*. It is of the investigations capable of being executed. In thought that this thickening is the forerunner of more particular, simultaneous estimation of cardiac output and advanced disease which leads to renal failure. renal blood flow, while extremely difficult in humans, is Retent clinical studies arc agreed in showing an increase in quite feasible in experimental animals, using the labelled the glomerular filtration rate (GFR) in early diabetes47. microsphere technique previously described10 This elevation of GFR is accompanied by normal or Previous work on experimental diabetes has been mainly slightly increased renal plasma flow (RPF) in some directed to the toxic effects of the diabetogenic spurns on reports14 and reduced RPF in others4. The exact the kidney itself. Alloxan and strcptbzoiocin were both mechanism behind this high GFR is not known. It has reported to cause renal lesions"'14. However, these lesions been variously suggested that it might be related to an were also shown to be due to the diabetic condition or to