The inverse square law: A basic principle in brachytherapy.

The purpose of this article is to remind the importance of the inverse square law in radiotherapy and especially in brachytherapy. Indeed, beyond the impact in radiation therapy with high energy beam, there is the use of radionuclides and low energy photons with short FSD where it is still more important. Comparisons between Iridium Brachytherapy and low energy X-rays brachytherapy show equivalent dose distributions in the first few centimeters. If the inverse square law is not the only element influencing the dose distributions calculations, it must not be forgotten. And it is playing a major role in brachytherapy with short FSD (<6cm).

Contact X-ray brachytherapy for rectal cancer: Past, present, and future.

The Papillon experience and the Lyon R96-02 trial have shown that contact X-ray brachytherapy of 50kV is efficient and safe to achieve long term local control and organ preservation for cT1 and early cT2-3 rectal cancers. The OPERA trial, using the Papillon 50™ machine, brings further support to this preservation strategy for selected T2T3ab lesions. Future trials using a contact X-ray boost will try to consolidate and enlarge its place in organ preservation for rectal cancers.

A brief history of contact X-ray brachytherapy 50 kVp.

Contact X ray brachytherapy 50 kVp was initiated in the 1930s with the Siemens unit and popularized with the Philips unit in the 1950s. A renaissance was seen in the early 2000s with the Intrabeam™ unit for breast IORT. Presently the Papillon™ systems thanks to its high dose rate (>10Gy/mn) can be used to treat breast (IORT), skin, eyelid and rectal cancers. Future developments are expected to consolidate the place of contact radiotherapy as a safe and efficient treatment for accessible early tumors.

A systematic literature mapping and meta-analysis of animal-based traits as indicators of production diseases in pigs.

The choice of animal-based traits to identify and deal with production diseases is often a challenge for pig farmers, researchers and other related professionals. This systematic review focused on production diseases, that is, the diseases that arise from management practices, affecting the digestive, locomotory and respiratory system of pigs. The aim was to classify all traits that have been measured and conduct a meta-analysis to quantify the impact of diseases on these traits so that these can be used as indicators for intervention. Data were extracted from 67 peer-reviewed publications selected from 2339 records. Traits were classified as productive (performance and carcass composition), behavioural, biochemical and molecular traits. A meta-analysis based on mixed models was performed on traits assessed more than five times across studies, using the package metafor of the R software. A total of 524 unique traits were recorded 1 to 31 times in a variety of sample material including blood, muscle, articular cartilage, bone or at the level of whole animal. No behavioural traits were recorded from the included experiments. Only 14 traits were measured on more than five occasions across studies. Traits within the biochemical, molecular and productive trait groups were reported most frequently in the published literature and were most affected by production diseases; among these were some cytokines (interleukin (IL) 1-ß, IL6, IL8 and tumour necrosis factor-α), acute phase proteins (haptoglobin) and daily weight gain. Quantification of the influence of factors relating to animal characteristics or husbandry practices was not possible, due to the low frequency of reporting throughout the literature. To conclude, this study has permitted a holistic assessment of traits measured in the published literature to study production diseases occurring in various stages of the production cycle of pigs. It shows the lack of consensus and common measurements of traits to characterise production diseases within the scientific literature. Specific traits, most of them relating to performance characteristics or immunological response of pigs, are proposed for further study as potential tools for the prognosis and study of production diseases.

Matrix metalloproteinase-19 is highly expressed in active multiple sclerosis lesions.

Matrix metalloproteinases (MMPs) are proteases known for their capacity to degrade extracellular matrix (ECM) components. MMPs have been implicated in several central nervous system (CNS) diseases, including multiple sclerosis (MS). Microarray analysis has demonstrated significant increased mRNA levels of MMP-19 in chronic MS lesions, suggesting a role of MMP-19 in MS pathogenesis. Therefore, in this study, we investigated the expression pattern and cellular localization of MMP-19 protein in various well-characterized MS lesion stages. In normal control patient white matter, MMP-19 was constitutively expressed by microglia throughout the brain parenchyma, suggesting a physiological role for this MMP family member. Likewise, MMP-19 was expressed by microglia in (p)reactive MS lesions, albeit more intense. In highly active demyelinating MS lesions, parenchymal and perivascular myelin-laden macrophages were strongly immunoreactive for MMP-19, whereas reactive astrocytes were occasionally immunopositive. Astrocytes in chronic inactive lesions were weakly stained for MMP-19. In vitro, MMP-19 was expressed in cultures of primary human microglia, not in astrocyte cultures. As MMP-19 is able to degrade basement membrane constituents and other ECM proteins, it is conceivable that this relatively novel MMP family member contributes to MS pathology by remodelling the ECM of the CNS, thereby influencing leucocyte infiltration, axonal regeneration and astrogliosis.

Influence of dietary protein level and source on the course of protein digestion along the small intestine of the veal calf.

The objective of this study was to examine the effect of the dietary crude protein (CP) content and source on the distribution of digesta proteins and peptides according to their molecular mass along the small intestine of veal calves. Diets contained 14, 104, 205, and 279 g/kg of CP supplied by skim milk powder (SMP) in experiment 1. Diets contained only SMP or SMP plus proteins (1:1 on digestible CP basis) from either a soybean protein concentrate (SPC), an isolated soy protein partially hydrolyzed (HSPI), or a potato protein concentrate (PPC) in experiment 2. Duodenal, jejunal, and ileal digesta were collected from calves fitted with simple cannulae and continuously infused the milk replacers into the abomasum. The distribution of molecular mass (Mr) of proteins and peptides was studied by gel filtration chromatography. Increasing the dietary CP level of milk replacers increased the flow of oligopeptides and free amino acids in ileal digesta. Incorporating plant protein increased the flow of proteins with Mr > 20,000 in the duodenum and that of proteins and peptides with Mr < 10,000 in the ileum. Hydrolysis of oligopeptides and absorption may be a limiting step in the digestion of plant protein in the veal calf.

The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis.

In multiple sclerosis, matrix metalloproteinases (MMPs) are effectors of crucial pathogenetic steps, such as blood-brain barrier breakdown, invasion of brain parenchyma by immune cells and demyelination. However, only limited data are available on the types of MMPs induced in the course of multiple sclerosis, and on the role of their endogenous antagonists, the tissue inhibitors of metalloproteinases (TIMPs). We quantified the transcriptional expression of six MMPs and the four TIMPs in lesions and in normal appearing white matter (NAWM) from post-mortem multiple sclerosis brain tissue by real-time polymerase chain reaction, and compared levels with those in brain tissue from six control patients without neurological disease. The mRNA expression of MMP-7 and -9, but not of other metalloproteinases [MMP-2 and -3, and tumour necrosis factor (TNF)-alpha-converting-enzyme] was equally upregulated throughout all stages of lesion formation with active inflammation, and in most of matched NAWM tissue. The transcription of cytokines TNF-alpha/beta and IL (interleukin)-2, known modulators of MMPs, was upregulated only in distinct stages of lesion formation, while their receptors were not induced at all, which suggests that additional signalling molecules participate in the sustained upregulation of MMP-7 and -9 in multiple sclerosis. None of the TIMPs showed a significant induction over baseline expression of controls. We hypothesize that an imbalance between MMP and TIMP expression may cause a persistent proteolytic overactivity in multiple sclerosis, that may be a factor for continuous tissue destruction, and hence for secondary disease progression.

Isolation and characterization of adult microglial cells and oligodendrocytes derived from postmortem human brain tissue.

The present study provides a detailed description of the simultaneous establishment and immunocytochemical characterization of highly enriched human adult microglial cell cultures as well as of oligodendrocyte cultures. For this study, brain tissue specimens were collected at autopsy with relatively short postmortem times (3-9 h) from various regions of the CNS of Alzheimer's disease, Pick's disease and non-demented control cases. Although methods to isolate viable glial cells from human adult brain tissue have been described, these human brain specimens were often derived from surgical resections, i.e., in order to treat intractable epilepsy, brain tumors or cardiovascular diseases involving the brain. However, for the study of many neurological disorders, surgical material is not available. Furthermore, for obvious reasons, there is a limit to the number of central nervous system (CNS) regions from which (enough) tissue can be obtained at surgery. The adherent primary microglial cells, isolated according to the here described procedures consisted of proliferating, phagocytotic cells that expressed various microglia/macrophage-specific markers as judged by immunocytochemical analysis. Non-adherent cells isolated from the same brain tissue samples expressed oligodendrocyte-specific markers. The current described culture system may provide a valuable tool in studying human CNS biology and disease.

Morphology and enzyme activities of the small intestine are modulated by dietary protein source in the preruminant calf.

A study was undertaken to assess the impact of the protein nature and soya antigenicity on the morphology and some enzyme activities of the jejunum in preruminant calves. Twenty Holstein calves fitted with a duodenal cannula were fed a liquid diet based on skimmed milk powder (SMP) for 2 weeks. They were then switched onto diets containing a mixture of SMP and either antigenic heated soybean flour (HSF; n = 12) or hypo-antigenic soya protein concentrate (SPC; n = 8) for 8 weeks, after which they were reverted back to the SMP diet for 2 weeks. The diets contained similar amounts of digestible nitrogen and energy, and were fed at a rate of 55 g DM/kg(0.75)/d. Proximal jejunal biopsies were collected just before (week 0), during (weeks 2 and 8) and after (week 10) feeding of the soya-based diets, and were used for morphology measurements and the determination of total alkaline phosphatase, lactase, amino-peptidases A and N, and dipeptidyl peptidase IV activities. Feed intake and growth were similar between the HSF and SPC groups during the experimental period. The effects of antigenicity and the antigenicity x time interaction were never significant (P > 0.05). Villus height decreased (P < 0.01) between weeks 0 and 2, and increased (P < 0.05) between weeks 8 and 10. Villus width increased between weeks 2 and 8 (P < 0.001). Crypt depth also increased between weeks 0 and 2 (P < 0.001). Specific activities of alkaline phosphatase (P < 0.01) and amino-peptidase N (P < 0.05) decreased between weeks 0 and 2. Conversely, those of alkaline phosphatase (P < 0.0001), lactase (P < 0.01) and dipeptidyl-peptidase IV (P < 0.0001) increased between weeks 8 and 10. Specific activities for lactase and amino-peptidase N decreased (P < 0.01) between weeks 2 and 8. The treatments had little effects on the amino-peptidase A activity. In conclusion, the present work demonstrated that soybean protein markedly depressed the morphology and most enzyme activities of the calf small intestine. On the contrary, the in vitro antigenicity of soybean protein had little influence on these parameters in this study.

Expression of transforming growth factor (TGF)-beta1, -beta2, and -beta3 isoforms and TGF-beta type I and type II receptors in multiple sclerosis lesions and human adult astrocyte cultures.

It is known that the pleiotropic cytokine transforming growth factor beta (TGF-beta) has a regulatory role in the process of tissue repair and remodelling following injury. As reports on these molecules in multiple sclerosis (MS) lesion with different lesional activity are rare, we studied the cellular localization of TGF-beta1, -beta2, and -beta3 isoforms, and TGF-beta receptor type I (TGF-betaR-I) and TGF-betaR-II expression by immunohistochemistry on postmortem brain tissue from MS and normal control cases. To validate the TGF-beta staining results we demonstrated that cultured human adult astrocytes that produce biological active TGF-beta2, and to a lesser extent TGF-beta1, were immunoreactive for all 3 TGF-beta isoforms. Moreover, at mRNA level TGF-beta1 was detected in MS and normal control brain tissue. In normal control brain tissue, TGF-beta isoforms were expressed in ramified microglia and TGF-beta2, and -beta3 on neuronal cells in the gray matter TGF-betaR-I and TGF-betaR-II expression was found on endothelial cells, astrocytes, microglia, and neurons. In active demyelinating MS lesions a strong to intense immunoreactivity was detected for all 3 TGF-beta isoforms in perivascular and parenchymal (foamy) macrophages and in hypertrophic astrocytes. Strong immunoreactivity for TGF-betaR-I and TGF-betaR-II was found on macrophages in both parenchymal and perivascular areas and on hypertrophic astrocytes and endothelial cells in active demyelinating MS lesions. In chronic active and inactive MS lesions, all 3 TGF-beta isoforms and their receptors were strongly expressed in hypertrophic astrocytes. Our findings strongly suggest that the expression of the various TGF-beta isoforms and their receptor types found in MS lesions with different cellular activity participate in reactive processes leading to the formation of chronic MS lesions.