Islet amyloid deposition limits the viability of human islet grafts but not porcine islet grafts.

Islet transplantation is a promising treatment for diabetes but long-term success is limited by progressive graft loss. Aggregates of the beta cell peptide islet amyloid polypeptide (IAPP) promote beta cell apoptosis and rapid amyloid formation occurs in transplanted islets. Porcine islets are an attractive alternative islet source as they demonstrate long-term graft survival. We compared the capacity of transplanted human and porcine islets to form amyloid as an explanation for differences in graft survival. Human islets were transplanted into streptozotocin-diabetic immune-deficient mice. Amyloid deposition was detectable at 4 weeks posttransplantation and was associated with islet graft failure. More extensive amyloid deposition was observed after 8 weeks. By contrast, no amyloid was detected in transplanted neonatal or adult porcine islets that had maintained normoglycemia for up to 195 days. To determine whether differences in IAPP sequence between humans and pigs could explain differences in amyloid formation and transplant viability, we sequenced porcine IAPP. Porcine IAPP differs from the human sequence at 10 positions and includes substitutions predicted to reduce its amyloidogenicity. Synthetic porcine IAPP was considerably less amyloidogenic than human IAPP as determined by transmission electron microscopy, circular dichroism, and thioflavin T binding. Viability assays indicated that porcine IAPP is significantly less toxic to INS-1 beta cells than human IAPP. Our findings demonstrate that species differences in IAPP sequence can explain the lack of amyloid formation and improved survival of transplanted porcine islets. These data highlight the potential of porcine islet transplantation as a therapeutic approach for human diabetes.

[Globoid cell leukodystrophy of adult. A first case in Poland]. / Leukodystrofia globoidalna doroslych. Pierwszy przypadek w Polsce.

Krabbe disease (globoid cell leukodystrophy) is a progressive, autosomal recessive disorder affecting peripheral and central nervous system. This disease is associated with mutation in GALC gene and its locus has been mapped to chromosome 14q31. GALC gene codes lysosomal hydrolytic enzyme: galactocerebroside ß-galactosidase (galactosylceramidase) which is crucial for degradation of galactolipids, mostly galactosylceramide and galactosylsphingosine (psychosine). The disease may be subdivided into four types: infantile form with onset within the first six months, child form presenting between 6 months and 3 years, juvenile form presenting between 3 and 10 years and the rarest adult form with onset after 10 years. The diagnosis of Krabbe disease is based on clinical findings and confirmed with galactocerebroside ß-galactosidase deficiency. We have found family with adult-onset disease. To our knowledge, this is the first observation of patient with adult form of Krabbe disease in Poland.

A randomized, double-blind, placebo-controlled, parallel-group, enriched-design study of nabiximols* (Sativex(®) ), as add-on therapy, in subjects with refractory spasticity caused by multiple sclerosis.

BACKGROUND: Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design. METHODS: A 19-week follow-up, multicentre, double-blind, randomized, placebo-controlled, parallel-group study in subjects with multiple sclerosis spasticity not fully relieved with current antispasticity therapy. Subjects were treated with nabiximols, as add-on therapy, in a single-blind manner for 4weeks, after which those achieving an improvement in spasticity of ≥20% progressed to a 12-week randomized, placebo-controlled phase. RESULTS: Of the 572 subjects enrolled, 272 achieved a ≥20% improvement after 4weeks of single-blind treatment, and 241 were randomized. The primary end-point was the difference between treatments in the mean spasticity Numeric Rating Scale (NRS) in the randomized, controlled phase of the study. Intention-to-treat (ITT) analysis showed a highly significant difference in favour of nabiximols (P=0.0002). Secondary end-points of responder analysis, Spasm Frequency Score, Sleep Disturbance NRS Patient, Carer and Clinician Global Impression of Change were all significant in favour of nabiximols. CONCLUSIONS: The enriched study design provides a method of determining the efficacy and safety of nabiximols in a way that more closely reflects proposed clinical practice, by limiting exposure to those patients who are likely to benefit from it. Hence, the difference between active and placebo should be a reflection of efficacy and safety in the population intended for treatment.

Impaired proinsulin processing is a characteristic of transplanted islets.

We sought to determine whether recipients of islet transplants have defective proinsulin processing. Individuals who had islet allo- or autotransplantation were compared to healthy nondiabetic subjects. Insulin (I), total proinsulin (TP), intact proinsulin and C-peptide (CP) were measured in samples of fasting serum by immunoassay, and the ratios of TP/TP+I and TP/CP were calculated. Islet allotransplant recipients had elevated TP levels relative to nondiabetic controls (16.8 [5.5-28.8] vs. 8.4 [4.0-21.8] pmol/L; p < 0.05) and autologous transplant recipients (7.3 [0.3-82.3] pmol/L; p < 0.05). Islet autotransplant recipients had significantly higher TP/TP+I ratios relative to nondiabetic controls (35.9 +/- 6.4 vs. 13.9 +/- 1.4%; p < 0.001). Islet allotransplant recipients, some of whom were on insulin, tended to have higher TP/TP+I ratios. The TP/CP ratio was significantly higher in both islet autotransplant (8.9 [0.6-105.2]; p < 0.05) and allotransplant recipients (2.4 [0.8-8.8]; p < 0.001) relative to nondiabetic controls (1.4 [0.5-2.6]%). Consistent with these findings, TP/TP+I and TP/CP values in islet autotransplant recipients increased significantly by 1-year posttransplant compared to preoperative levels (TP/CP: 3.8 +/- 0.6 vs. 23.3 +/- 7.9%; p < 0.05). Both allo- and autotransplant subjects who received <10,000 IE/kg had higher TP/CP ratios than those who received >10,000 IE/kg. Islet transplant recipients exhibit defects in the processing of proinsulin similar to that observed in subjects with type 2 diabetes manifest as higher levels of total proinsulin and increased TP/TP+I and TP/CP ratios.

Activity of selected enzymes in erythrocytes and level of plasma antioxidants in response to single whole-body cryostimulation in humans.

The influence of extremely low temperatures on the human body and physiological reactions is not fully understood. The aim of this research was to estimate the influence of a single exposure to cryogenic temperature (-130 degrees C), without subsequent kinesiotherapy, on the activity of the most crucial antioxidant enzymes in erythrocytes: superoxide dismutase (SOD), catalase (CAT), glutathione reductase (R-GSSG), glutathione peroxidase (GPx) and glutathione transferase (T-GSH). In the plasma, the concentrations of glutathione, uric acid, albumins and extra-erythrocyte haemoglobin as components of the non-enzymatic antioxidant system were evaluated. The subjects were 10 healthy young men. Blood was sampled in the morning on the day of cryostimulation, 30 min after cryostimulation and the next morning. The enzymatic response of the antioxidant defence to the influence of the extremely low temperature resulted in an immediate, significant, increase in GPx and R-GSSG activities, but a decrease in CAT and T-GSH activities. We observed an increase in the concentrations of all the examined non-enzymatic antioxidants, especially extra-erythrocyte haemoglobin and uric acid, which had both increased further the day after cryostimulation. The results indicate that a single stimulation with cryogenic temperatures results in oxidative stress in a healthy body, but that the level of stress is not very high. It seems that in this case the most significant role in the antioxidant mechanisms is played by peroxidase.

Epidermal growth factor in human cerebrospinal fluid: reduced levels in amyotrophic lateral sclerosis.

Epidermal growth factor (EGF), a mitogenic peptide, is widely distributed within the brain and endocrine cells of the gastro-intestinal tract. Using EGF radioreceptor assay, the EGF level was measured in lumbar cerebrospinal fluid from five patients with amyotrophic lateral sclerosis (ALS) and seven patients with intervertebral disc disease as a control group. The patients with ALS showed reduced EGF levels to 662.4 +/- 207 pg/ml as compared with controls 1013 +/- 182.8 pg/ml (P less than 0.02). These results indicate a possible EGF involvement in the pathogenesis of ALS.

Creutzfeldt-Jakob disease: ultrastructural study of brain biopsy: unusual interaction between astrocytes and oligo- and microglia.

We report a case of Creutzfeldt-Jakob (CJD) disease in a 72-year-old man without characteristic EEG alterations. Unusually abundant pleomorphic PrP-immunopositive amyloid plaques were found in the cerebellum. Despite of this similarity with Gerstmann-Straussler-Scheinker (GSS) disease the case cannot be classified as GSS lacking classical GSS 102 PRNP gene mutation. The ultrastructural findings were similar to those described previously for CJD. The close contact of reactive astrocytes with both oligodendroglia and microglia in this case suggests their possible functional interaction.

The immunohistochemistry and ultrastructure of ganglioglioma with chromosomal alterations: a case report.

Ganglioglioma, together with its counterparts-ganglioneuroma and gangliocytoma are relatively uncommon neoplasms of the brain composed of neoplastic neurons (ganglion and ganglioid cells) and glial cells. We report here a case of ganglioglioma studied by electron microscopy. The case was further characterized by peculiar chromosomal alterations, 46,XX[6]/43,XX[1], der(1)t(1;5)(q21;q12), der(8;13)(q10;q10),-9,i(10)(q10). Routine light microscopy revealed mixed neuro-glial tumor composed of pilocytic astrocytes with abundant Rosenthal fibers and relatively numerous ganglion cells. The latter were immunoreactive with antibodies (Abs) against synaptophysin and neurofilament protein (NFP). Anti-NFP Abs also immunostained numerous distorted axons embedded in the tumor mass. Some of these showed bullous swellings and thus were analogous to dystrophic neurites or spheroids. Ganglion cells were characterized by abundant intracytoplasmic dense-core vesicles, absence of intermediate filaments and numerous microtubules. Occasionally a close apposition of ganglion cells and Rosenthal fibers were seen. Dense-cored vesicles were pleomorphic and ranged in diameter from small synaptic vesicles to large lysosome-like neurosecretory granules. The former occasionally formed characteristic dumbbell shapes. Neoplastic astrocytes were identical to those of other glial tumors of astrocytic lineage; numerous Rosenthal fibers were frequently seen.

[Dipyridamole as an inhibitor of vaccinia virus replication]. / Dipiridamol kak ingibitor razmnozheniia virusa vaktsiny.

Dipyridamole in concentration of 25 microM inhibited the multiplication of vaccinia virus in about 90% of cells. In the presence of this substance, [3H]-uptake was sharply reduced both in uninfected and infected RK13 cells, while [14C]-uptake was not inhibited incorporation of [3H]-thymidine and [14C]-amino acids into viral particles. The present findings suggest that the antiviral character of dipyridamole is related with the inhibition of the substrate transport through the cell membrane.

[Case of Frankl-Hochwart syndrome (polyneuritis cranials menieriformis)]. / Przypadek zespolu Frankl-Hochwarta polineuritis cranialis menieriformis).

In a 19-year-old man sudden Bell's palsy developed and after 2 days vertigo and peripheral-type nystagmus supervened. ENG demonstrated presence of spontaneous nystagmus on right gaze and lack of excitability of the left horizontal canal. The cerebrospinal fluid was normal, virological examination failed to demonstrate presence of antibodies to zoster virus or a rise of antibodies to enteroviruses. Vertigo and nystagmus disappeared within several days. Bell's palsy regressed later. The results of virological investigations cast doubt on the views of these authors who regard Frankl-Hochwart syndrome as a variety of Ramsay Hung Syndrome. In the presently reported case the possibility of zoster virus being the cause of the disease has been ruled out.

[Immunoglobulins and the complement system in Horton's headache]. / Badania immunoglobulin i uklladu dopellniacza w bólu gllowy Hortona.

In 39 patients with Horton's headache (bgh) and 70 controls the total complement level and the levels of its C3 and C4 fractions, as well as IgG, IgA and IgM levels were determined. It was found that in bgh patients the mean level of the C3 fraction was significantly below that in the control group, while the C4 level was still within normal range. The levels of immunoglobulins were not statistically significantly different in these groups with the exception of IgA which was significantly lower in bgh cases. The author thinks that low C3 fraction level may be a part of the clinical pattern of bgh and is due to activation of the complement system on the alternative pathway. On the other hand, bgh attacks could not be qualified into any known type of allergic reaction.

[Blood testosterone levels in patients with Horton's headache]. / Poziom testosteronu we krwi chorych z bólem glowy Hortona.

Serum testosterone level was determined by radioimmunoassay in 57 men, including 23 cases of Horton's neuralgia during the period of recurrent headaches but not during an attack of headache, in 10 cases of trigeminal neuralgia, 10 cases of radicular pain and in 14 blood donors. Only in the blood donors this level was normal, in the remaining cases it was statistically significantly decreased, especially in cases of radicular pains. The author believes that in the period of Horton's headaches the testosterone level is decreased due to recurrent attacks of pain and not due to a process involving the hypothalamus.

["Cluster-tic syndrome" with a report of our case]. / Zespól "cluster-tic" z opisem wlasnego przypadku.

The author describes a case with elements of trigeminal neuralgia coexistent with Horton's headaches, with predominance of the latter ones. For this syndrome the author proposes the name "cluster-tic". In the pathogenesis of headache attacks of Horton's type and neuralgia of the V nerve the mediation of neurotransmitters and the nosological position of the described syndrome are discussed.

[Electroencephalographic studies of 100 cases of migraine (control groups included)]. / Badania elektroencefalograficzne w 100 przypadkach migreny (z uwzglednienim grup kontrolnych)

The investigations were done in a group of 100 patients with migraine, 50 patients with chronic diseases of various organs and 50 healthy subjects. EEG investigations in patients with migraine were carried out several times, in controls only once. The records were interpreted according to strictly defined criteria separating normal from pathological (slightly, moderately and severely) records. In 35% of migrainous patients slight or moderate changes were found. The frequency of these changes was significantly increased in relation to healthy subjects and approached the frequency found in non-neurological cases. EEG changes in migrainous patients failed to demonstrate any specific features and failed to correlate with clinical findings. The analysis of 330 EEG records in 100 cases of migraine demonstrated that some records changed in time and that the number of records showing deterioration was greater than that of records showing improvement.

[Chronic Horton's neuralgia treated successfully with indomethacin]. / Przypadek przewleklej postaci bólu glowy Hortona leczony pomyslnie indometacyna (metindolem)

The author describes a case in which different types of headaches occurred in life. In childhood the patient had typical attacks of ophthalmic migraine, at the age of 45 years classical Horton's neuralgia developed lasting 5 months, occurring 3-4 times daily and 2-3 times in night time. The pains were intense, their location was always identical and their duration was 15-20 min. It seemed at the time of observation that they represented a form intermediate between that described by Ekbom and Olivarius and that reported by Sjaastad and Dale. After treatment with Indomethacin immediate improvement was obtained with disappearance of pains.

[The myasthenic syndrome after chloroquine]. / Zespól miasteniczny po stosowaniu arechiny.

The author presents a case of a 52-year old woman who suffered from dermatitis seborrhoica. She was treated with chloroquine. During the third month of treatment with chloroquine the symptoms of myasthenia appeared and led to hospitalization. The neurological and additional examinations confirmed the diagnosis. Four days after withdrawal of chloroquine treatment the myasthenic symptoms began to disappear and they finally ceased after two weeks. At this all other drugs were also withdrawn. The control examination after two months showed normal neurological status.

[Treatment of Horton's headache with testosterone]. / Leczenie bolu glowy Hortona przy pomocy testosteronu.

The studied material comprised 15 men with 12 of them having the episodic from of Horton's headaches and 3 with chronic form. In the episodic form the age of the patients was from 32 to 48 years, mean age 38. The history of the disease was from 6 to 12 years, the duration of a spell of headaches was 2-3 months and the patients had then 2-5 attacks of pain daily. Before the onset of treatment the patients were not given for 1 week any drugs or placebo. After determination of the index of attacks treatment was begun. For 7-10 days the patients received daily intramuscular testosterone propionate 25 mg, and then 10 mg for a similar time period. Before the treatment the index of attacks was 3.66 (with the total number of attacks 308). In the first week of treatment it decreased to 1.11 (94 attacks), in the second week it was 0.16 and in the third week 0.05. In 10 patients the attacks disappeared completely (83%), in the remaining 2 ones they regressed in a later time. Three patients with the chronic form received this treatment without effect.

[Xylose test in patients with attacks of headaches (migraine, Horton's headache)]. / Test ksylozowy u chorych z napadowymi bólami glowy (migrena, ból glowy Hortona).

The aim of this work was to study digestive tract function by means of xylose test in patients with attacks of headaches. The investigations were carried out in 14 patients with migraine, 10 with Horton's headache and 1 patient with both these conditions. In patients with migraine or Horton's headache the xylose test was normal in 65% of cases, in the remaining 35% (8 patients, 4 in each group) xylose elimination was abnormal, because it was below 30%. The authors discuss the factors which could influence the abnormal results of xylose test in these patients, since they had no signs of other diseases than the mentioned headaches.

[SUNCT syndrome--case report]. / Zespól SUNCT--opis przypadku.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tears (SUNCT) syndrome is a very rare disorder, first described by Sjaastad et al. in 1989. The authors report a case of that type of headache in an 80 years old woman. They also discuss the pathophysiology and treatment.

[Traumatic injury of ciliary ganglion]. / Urazowe uszkodzenie zwoju rzeskowego

The authors report a case in which slight cranial trauma was followed by manifestations of damage to the right ciliary ganglion. After 3 weeks the signs of damage began to regress and disappeared completely. Laboratory investigations failed to demonstrate any abnormalities. Apart from this trauma there were no other detectable causes, and especially there were no history data suggesting past infection, botulism or syphilis. The mechanism of ciliary ganglion injury is not known (contusion, haematoma, oedema etc.).