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Background: Plant-based remedies have been used since antiquity to treat menstrual-related diseases (MD). From the late nineteenth to the early to mid-twentieth century, Italian folk remedies to treat "women's diseases" were documented in a vast corpus of literature sources. Aim: The purpose of this paper is to bring to light the plant-based treatments utilized by Italian folk medicine to heal clinical manifestations of premenstrual syndrome (PMS), dysmenorrhea, amenorrhea and menstrual disorders in an attempt to discuss these remedies from a modern pharmacological point of view. Moreover, we compare the medical applications described by Hippocrates with those utilized by Italian folk medicine to check if they result from a sort of continuity of use by over two thousand years. Results: Out of the 54 plants employed in Italian folk medicine, 25 (46.3%) were already documented in the pharmacopoeia of the Corpus Hippocraticum for treating MD. Subsequently, a detailed search of scientific data banks such as Medline and Scopus was undertaken to uncover recent results concerning bioactivities of the plant extracts to treat MD. About 26% of the plants used by Italian folk medicine, nowadays, have undergone human trials to assess their actual efficacy. At the same time, about 41% of these herbal remedies come back to in different countries. Conclusions: Active principles extracted from plants used by Italian folk healers could be a promising source of knowledge and represent strength candidates for future drug discovery for the management of MD.
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ETHNOPHARMACOLOGICAL RELEVANCE: Before the advent of modern antibiotics, microbial infections were treated with herbal medicine or cauterization. Literature from the latter half of the nineteenth to the early mid-twentieth century, when antibiotics became widely available, arguably holds the most progressive information about herbal remedies to treat bacterial skin diseases. The corpus of literature produced in Italy during that period is not easily accessible and mostly out of print. MATERIAL AND METHODS: Plant-based remedies utilized in popular Italian medicine to treat anthrax, boils, erysipelas, impetigo, pustules, and whitlow were sourced from literature indexed in and available through the National Library Service website of the Italian Libraries Network. The remedies are assessed for their antimicrobial potential based on a detailed search of the herbal drug species in scientific databases. RESULTS: A considerable part of the reviewed recipes included specific excipients (41 out of 139) and others were produced with fresh plant material (48 out of 139). Out of the 52 identified herbal drug species used in popular Italian medicine against dermatologic infections, extracts of 43 were shown to have moderate in vitro activity against Gram-positive and Gram-negative bacteria. CONCLUSION: The antibacterial activity of the extracts and pure compounds as reported in the reviewed literature is mostly based on in vitro assays and generally does not encourage follow up studies. The effectiveness of the reported recipes, which include fresh plant material and excipients can only be assessed through in vivo studies. Those remedies including herbal drugs with reported antimicrobial activity might have the potential as complementary therapies. The reviewed plant based antimicrobial recipes might serve as inspirations in the search for alternative topical antibacterial strategies and the search for their synergistic and potentiating ingredients.
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Antibacterianos/uso terapéutico , Medicina Tradicional/historia , Fitoterapia/historia , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Italia , Preparaciones de Plantas/uso terapéuticoRESUMEN
AIM: CADASIL is an inherited cerebrovascular disease caused by mutations in the NOTCH3 gene. Notch signaling is involved in a broad spectrum of function, from the cell proliferation to apoptosis. Thus far, because the molecular mechanism underlying the pathological alterations remains unclear and taking into account that fibroblasts contribute to the integrity of the vasculature, our aims was to establish whether fibroblasts, in subjects carrying different NOTCH3 mutations, show abnormalities in the protein expression. METHODS: We performed the investigation on skin fibroblasts in culture obtained from three CADASIL patients and normal subjects. The patients were genetically characterized, and carried a p.R61W, a p.C174T, and p.R103X, mutation respectively. Notch3 expression was first evaluated on fibroblasts by immunofluorescence analysis, then western blot on cellular extract was utilized to validate the immunofluorescence results. RESULTS: The Notch3 immunoreactivity was clearly detected along the cellular body and in the cellular nuclei of the control fibroblasts. We observed a marked, statistically significant, reduction of the fluorescence immunoreactivity in the fibroblasts from patient with the classical C174T cysteine mutation and a less pronounced reduction in the other two subject's samples with respect to the normal controls. These data were confirmed by the immunoblot analysis. CONCLUSIONS: Our results show that the investigated three NOTCH3 mutations are associated with a reduction of the levels of Notch3 expression in vitro. Because the smooth muscle cells appear to be predominantly involved in this cerebrovascular disease, our result, despite the limitation of the sample size examinated, clearly suggest that also fibroblasts, directly involved in making the vascular basal lamina and in maintaining the vascular integrity, may play an important role in the mechanism responsible for the disease.
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CADASIL/metabolismo , Fibroblastos/metabolismo , Receptor Notch3/metabolismo , Piel/metabolismo , Adulto , Anciano , Western Blotting , CADASIL/genética , CADASIL/patología , Células Cultivadas , Femenino , Fibroblastos/patología , Técnica del Anticuerpo Fluorescente , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Mutación , Cultivo Primario de Células , Receptor Notch3/genética , Piel/patologíaRESUMEN
BACKGROUND: Headache has been recognized since antiquity. From the late nineteenth to the early to mid-twentieth century, Italian folk remedies to treat headache were documented in a vast corpus of literature sources. AIM: The purpose of this paper is to bring to light the plant-based treatments utilized by Italian folk medicine to heal headache in an attempt to discuss these remedies from a modern pharmacological point of view. Moreover, we compare the medical applications described by Hippocrates, Pliny the Elder, Dioscorides, Galen and Serenus Sammonicus with those utilized by Italian folk medicine to check if they result from a sort of continuity of use by over two thousand years. RESULTS: A detailed search of the scientific data banks such as Medline and Scopus was undertaken to uncover recent results concerning the anti-inflammatory, anti-nociceptive and analgesic activities of the plants. Fifty-eight (78.4%) plant-based remedies have shown in vivo, in vitro or in human trials a large spectrum of anti-inflammatory, anti-nociceptive and analgesic activities. Moreover, thirty-one of remedies (41.9%) were already included in the pharmacopoeia between the 5th century BC and the 2nd century AD. CONCLUSION: Italian folk medicine could be a promising source of knowledge and could provide evidences for active principles that have not as of yet been fully used for their potential.
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Cefalea/tratamiento farmacológico , Medicina Tradicional/historia , Preparaciones de Plantas/historia , Plantas Medicinales/química , Animales , Cefalea/historia , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Italia , Fitoterapia/historia , Preparaciones de Plantas/administración & dosificaciónRESUMEN
Stroke is the third leading cause of death worldwide after heart disease and all forms of cancers. Monogenic disorders, genetic, and environmental risk factors contribute to damaging cerebral blood vessels and, consequently, cause stroke. Developments in genomic research led to the discovery of numerous copy number variants (CNVs) that have been recently identified as a new tool for understanding the genetic basis of many diseases. This review discusses the current understanding of the types of stroke, the existing knowledge on the involvement of specific CNVs in stroke as well as the limitations of the methods used for detecting CNVs like SNP-microarray. To confirm an unequivocally association between CNVs and stroke and extend the current findings, it would be desirable to use another methodology to detect smaller CNVs or CNVs in genomic regions poorly covered by this technique, for instance, CGH-array.
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Variaciones en el Número de Copia de ADN/genética , Genoma Humano/genética , Accidente Cerebrovascular/genética , Hibridación Genómica Comparativa , Genotipo , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Accidente Cerebrovascular/clasificaciónRESUMEN
Copper-zinc superoxide dismutase-1 (SOD1) is the second most common mutated gene in amyotrophic lateral sclerosis (ALS). To date more than 150 missense mutations of SOD1 have been reported. The objective of this study was to describe a novel SOD1 mutation and its phenotypic expression. We describe a 74-year-old Caucasian man who began to complain of progressive weakness and atrophy of the right hand and over 10 months developed a severe tetraparesis, with atrophies of upper and lower limbs and neck muscles, dysphagia, and dyspnea that led to percutaneous endoscopic gastrostomy and tracheotomy. A diagnosis of ALS was made. Genetic analysis identified a heterozygous mutation in exon 4 of SOD1 that results in the amino acid substitution from arginine to cysteine at position 115 (p.R115C). We identified a novel pathogenic SOD1 mutation in a patient with a very rapid disease progression and aggressive phenotype providing additional information on the wide range of SOD1 mutations in apparently sporadic ALS and confirming the possibility of a strong genotype-phenotype correlation for distinct SOD1 mutations.
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Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/genética , Mutación Missense/genética , Superóxido Dismutasa/genética , Anciano , Esclerosis Amiotrófica Lateral/patología , Progresión de la Enfermedad , Tamización de Portadores Genéticos , Humanos , Masculino , Superóxido Dismutasa-1RESUMEN
OBJECTIVE: Recent evidence suggests that intermediate-length polyglutamine (PolyQ) expansions in the ataxin-2 (ATXN-2) gene are a risk factor for amyotrophic lateral sclerosis (ALS). This work was undertaken with the aim to investigate the frequency of ataxin-1 (ATXN-1) and ATXN-2 PolyQ expansions in a cohort of patients with sporadic ALS (sALS) and patients with familial ALS (fALS) from southern Italy. METHODS: We assessed the PolyQ lengths of ATXN-1 and ATXN-2 in 405 patients with sALS, 13 patients with fALS, and 296 unrelated controls without history of neurodegenerative disorders. RESULTS: We found significantly higher intermediate PolyQ expansions ≥ 32 for ATXN-1 alleles and ≥ 28 for ATXN-2 alleles in the sALS cohort (ATXN-1: ALS, 7.07% vs controls, 2.38%; p = 0.0001; ATXN-2: ALS, 2.72% vs controls, 0.5%; p = 0.001). ATXN-1 CAT and ATXN-2 CAA interruptions were detected in patients with ALS only. Age at onset, site of onset, and sex were not significantly related to the ATXN-1 or ATXN-2 PolyQ repeat length expansions. CONCLUSIONS: Both ATXN-1 and ATXN-2 PolyQ intermediate expansions are independently associated with an increased risk for ALS.
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Esclerosis Amiotrófica Lateral/genética , Proteínas del Tejido Nervioso/genética , Proteínas Nucleares/genética , Péptidos/genética , Expansión de Repetición de Trinucleótido , Adulto , Factores de Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Alelos , Ataxina-1 , Ataxinas , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Italia , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The routine molecular test for spinal muscular atrophy (SMA) diagnosis is based on the detection of a homozygous deletion of exons 7 and 8 of the telomeric copy of the survival motor neuron gene (SMN1). The presence of the centromeric copy of the SMN gene (SMN2) does not allow the detection of the hemizygous absence of the SMN1 gene, which characterizes the disease carriers. The demand for a quantitative SMN1 test is permanently growing because there is a high incidence of carriers. The disease is severe and to date there are no effective pharmacological treatments. Here, we present a non-radioactive assay based on real time quantitative polymerase chain reaction. We analyzed eight SMA patients, 14 SMA relatives and 50 health individuals from Southern Italy by real time quantitative method in order to identify haploid deletion occurring in SMA carriers. SMN1 copy number was determined by the comparative threshold cycle method (ΔΔCt). The results confirmed the deletion in all homozygous patients and permitted an evaluation of the number of alleles in the healthy carriers. This method is fast, reproducible, and enables us to discriminate carriers from healthy homozygous, which is impossible with normal techniques.
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Fused in sarcoma (FUS) or translocation in liposarcoma (TLS), a DNA/RNA-binding protein, causes a dominant autosomal inherited form of amyotrophic lateral sclerosis (ALS), ALS 6. Its main role in neurodegeneration is highlighted by the presence of cytoplasmic accumulation of its mutant protein form in ALS patients. To further define the frequency and spectrum of FUS gene mutations, we have performed a molecular screening of a cohort of 327 Italian patients from Southern Italy with sporadic ALS (SALS). We identified 4 patients carrying 3 different missense mutations and several polymorphisms. Two different substitutions occurring in the same amino acidic position have been observed in 2 patients: R521G and R521C respectively; P525L mutation has been found in 2 additional cases. Most of the patients with FUS mutations showed early symptom onset and had short disease survival. We also detected 4 different polymorphic variants (3'-untranslated region [UTR] variant, c.*41G>A; c.523+3ins[GAGGTG]; c.335-15del[TTTT]; and rs13331793) in 9 patients from within our cohort. This study underlines the importance of population-based mutation screening of newly identified genes.
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Esclerosis Amiotrófica Lateral/genética , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Proteína FUS de Unión a ARN/genética , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/fisiopatología , Análisis Mutacional de ADN , Exones/genética , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Examen NeurológicoRESUMEN
PURPOSE: Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder with an estimated incidence of one in 3,500 births. Clinically, NF1 is characterized by café-au-lait (CAL) spots, neurofibromas, freckling of the axillary or inguinal region, Lisch nodules, optic nerve glioma, and bone dysplasias. NF1 is caused by inactivating mutations of the 17q11.2-located NF1 gene. We present a clinical and molecular study of an Italian family with NF1. METHODS: The proband, a 10-year-old boy, showed large CAL spots and freckling on the axillary region and plexiform neurofibromas on the right side only. His father (47 years old) showed, in addition to the similar signs, numerous neurofibromas of various sizes on his thorax, abdomen, back, and shoulder. Two additional family members (a brother and a sister of the proband) presented only small CAL spots. The coding exons of NF1 gene were analyzed for mutations by denaturing high-performance liquid chromatography and sequencing in all family members. RESULTS: The mutational analysis of the NF1 gene revealed a novel frameshift insertion mutation in exon 4c (c.654 ins A) in all affected family members. This novel mutation creates a shift on the reading frame starting at codon 218 and leads to the introduction of a premature stop at codon 227. CONCLUSIONS: The segregation of the mutation with the affected phenotype and its absence in the 200 normal chromosomes suggest that it is responsible for the NF1 phenotype.
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Genes de Neurofibromatosis 1 , Neurofibromatosis 1/genética , Secuencia de Bases , Manchas Café con Leche/genética , Niño , Cromatografía Líquida de Alta Presión , Análisis Mutacional de ADN , Familia , Femenino , Mutación del Sistema de Lectura , Humanos , Italia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Reacción en Cadena de la PolimerasaRESUMEN
L-2-Hydroxyglutaric aciduria (L-2-HGA) is a neurometabolic disease characterized by the presence of elevated levels of 2-hydroxyglutaric acid in the plasma, cerebrospinal fluid and urine. Clinical features in this inherited condition consist of mental deterioration, ataxia and motor deficits with pyramidal and extrapyramidal symptoms and signs. L-2-HGA is caused by mutations in the L-2-HGDH gene which most probably encodes for a L-2-hydroxyglutarate dehydrogenase, a putative mitochondrial protein converting L-2-hydroxyglutarate to alphaketoglutarate. Here, we report a pathogenic nonsense mutation in the L-2-HGDH gene found for the first time in an Italian patient affected by L-2-HGA, reinforcing the previously described phenotype of this rare metabolic disease and confirming the data indicating that mutations in the L-2-HGDH gene cause L-2-HGA.
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Encefalopatías Metabólicas Innatas , Imagen de Difusión Tensora , Adulto , Encéfalo/patología , Encefalopatías Metabólicas Innatas/diagnóstico , Encefalopatías Metabólicas Innatas/genética , Encefalopatías Metabólicas Innatas/terapia , Análisis Mutacional de ADN , Homogentisato 1,2-Dioxigenasa/genética , Humanos , Italia , MasculinoRESUMEN
Mutations in the SPG4 gene are the most common causes of hereditary spastic paraplegia (HSP) accounting for up to 40% of autosomal dominant (AD) forms and 12-18% of sporadic cases. The phenotype associated with HSP due to mutations in the SPG4 gene tends to be pure. There is increasing evidence, however, of patients with complicated forms of spastic paraplegia in which SPG4 mutations were identified. A cohort of 38 unrelated Italian patients with spastic paraplegia, of which 24 had a clear dominant inheritance and 14 were apparently sporadic, were screened for mutations in the SPG4 gene. We identified 11 different mutations, six of which were novel (p.Glu143GlyfsX8, p.Tyr415X, p.Asp548Asn, c.1656_1664delinsTGACCT, c.1688-3C>G and c.*2G>T) and two exon deletions previously reported. The overall rate of SPG4 gene mutation in our patients was 36.8% (14/38); in AD-HSP we observed a mutation frequency of 45.8% (11/24), in sporadic cases the frequency was 21.4% (3/14). Furthermore, we found a mutational rate of 22.2% (2/9) and 41.4% (12/29) in the complicated and pure forms, respectively. The results underlie the importance of genetic testing in all affected individuals.
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Adenosina Trifosfatasas/genética , Paraplejía/genética , Regiones no Traducidas 3'/genética , Adolescente , Adulto , Anciano , Niño , Cromatografía Líquida de Alta Presión , Estudios de Cohortes , Análisis Mutacional de ADN , Exones , Femenino , Eliminación de Gen , Genotipo , Humanos , Italia , Masculino , Persona de Mediana Edad , Mutación Missense/genética , Fenotipo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Espastina , Adulto JovenAsunto(s)
CADASIL/genética , Cisteína/genética , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Polimorfismo de Nucleótido Simple/genética , Receptores Notch/genética , CADASIL/metabolismo , Exones/genética , Variación Genética/genética , Humanos , Intrones/genética , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Fenotipo , Receptor Notch3RESUMEN
Mutations in the Cu/Zn superoxide dismutase 1 (SOD1) gene have been reported to cause adult-onset autosomal dominant amyotrophic lateral sclerosis (FALS). In sporadic cases (SALS), de novo mutations in the SOD1 gene have occasionally been observed. All the SOD1 mutations are autosomal dominantly inherited with the exception of D90A. To date, in Italy, only two sporadic ALS cases carrying the D90A mutation have been reported in a homozygous state. We investigated for the presence of this mutation in 169 unrelated ALS patients from southern Italy. The genetic analysis revealed three ALS patients (1.8%) with mild phenotype carrying the homozygous D90A mutation.